rs41522944

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001114753.3(ENG):c.120C>T(p.Gly40Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00506 in 1,614,206 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 30)

Exomes 𝑓: 0.0052 ( 25 hom. )

Consequence

ENG
NM_001114753.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -1.03

Publications

1 publications found

Variant links:

Genes affected

ENG (HGNC:3349): (endoglin) This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds to the beta1 and beta3 peptides with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in preeclampsia and several types of cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]

ENG Gene-Disease associations (from GenCC):

telangiectasia, hereditary hemorrhagic, type 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, ClinGen
hereditary hemorrhagic telangiectasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
juvenile polyposis syndrome
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 9-127843193-G-A is Benign according to our data. Variant chr9-127843193-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 237016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.03 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00341 (519/152330) while in subpopulation NFE AF = 0.00563 (383/68026). AF 95% confidence interval is 0.00516. There are 2 homozygotes in GnomAd4. There are 222 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 519 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENG	NM_001114753.3 link	c.120C>T	p.Gly40Gly	synonymous_variant	Exon 2 of 15	ENST00000373203.9	NP_001108225.1	P17813-1Q96CG0A0A024R878
ENG	NM_000118.4 link	c.120C>T	p.Gly40Gly	synonymous_variant	Exon 2 of 14		NP_000109.1	P17813-2Q5T9B9
ENG	NM_001406715.1 link	c.120C>T	p.Gly40Gly	synonymous_variant	Exon 2 of 8		NP_001393644.1
ENG	NM_001278138.2 link	c.-427C>T		5_prime_UTR_variant	Exon 2 of 15		NP_001265067.1	P17813Q96CG0F5GX88B7Z6Y5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENG	ENST00000373203.9 link	c.120C>T	p.Gly40Gly	synonymous_variant	Exon 2 of 15	1	NM_001114753.3	ENSP00000362299.4		P17813-1

Frequencies

GnomAD3 genomes

AF:

0.00341

AC:

519

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00477

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00563

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00322

AC:

809

AN:

251452

AF XY:

0.00318

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00347

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00535

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00523

AC:

7645

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00503

AC XY:

3661

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.000836

AC:

AN:

33480

American (AMR)

AF:

0.00394

AC:

176

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000957

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00103

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00633

AC:

7040

AN:

1112008

Other (OTH)

AF:

0.00452

AC:

273

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

467

935

1402

1870

2337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00341

AC:

519

AN:

152330

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

41576

American (AMR)

AF:

0.00477

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00563

AC:

383

AN:

68026

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00463

Hom.:

Bravo

AF:

0.00353

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00616

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ENG: BP4, BP7, BS2 -

not specified

Benign:4

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Gly40Gly in exon 2 of ENG: This variant is not expected to have clinical signifi cance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.5% (44/8600) of Europ ean American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS; dbSNP rs41522944). -

Dec 02, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Telangiectasia, hereditary hemorrhagic, type 1

Benign:3

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Jun 30, 2014

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Hereditary hemorrhagic telangiectasia

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.3

(source)

DANN

Benign

0.86

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over