rs3739817

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001114753.3(ENG):c.1029C>T(p.Thr343Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 1,613,948 control chromosomes in the GnomAD database, including 6,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 440 hom., cov: 30)

Exomes 𝑓: 0.086 ( 6230 hom. )

Consequence

ENG
NM_001114753.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.80

Publications

25 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=-0.53).

BP6

Variant 9-127824409-G-A is Benign according to our data. Variant chr9-127824409-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.8 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENG	NM_001114753.3 link	c.1029C>T	p.Thr343Thr	synonymous_variant	Exon 8 of 15	ENST00000373203.9	NP_001108225.1	P17813-1Q96CG0A0A024R878
ENG	NM_000118.4 link	c.1029C>T	p.Thr343Thr	synonymous_variant	Exon 8 of 14		NP_000109.1	P17813-2Q5T9B9
ENG	NM_001278138.2 link	c.483C>T	p.Thr161Thr	synonymous_variant	Exon 8 of 15		NP_001265067.1	P17813Q96CG0F5GX88B7Z6Y5
ENG	NM_001406715.1 link	c.1029C>T	p.Thr343Thr	synonymous_variant	Exon 8 of 8		NP_001393644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENG	ENST00000373203.9 link	c.1029C>T	p.Thr343Thr	synonymous_variant	Exon 8 of 15	1	NM_001114753.3	ENSP00000362299.4		P17813-1

Frequencies

GnomAD3 genomes

AF:

0.0718

AC:

10922

AN:

152016

Hom.:

439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0484

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0676

Gnomad ASJ

AF:

0.0602

Gnomad EAS

AF:

0.0296

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.0832

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0807

Gnomad OTH

AF:

0.0680

GnomAD2 exomes

AF:

0.0897

AC:

22536

AN:

251224

AF XY:

0.0949

show subpopulations

Gnomad AFR exome

AF:

0.0448

Gnomad AMR exome

AF:

0.0889

Gnomad ASJ exome

AF:

0.0594

Gnomad EAS exome

AF:

0.0279

Gnomad FIN exome

AF:

0.0882

Gnomad NFE exome

AF:

0.0821

Gnomad OTH exome

AF:

0.0778

GnomAD4 exome

AF:

0.0863

AC:

126174

AN:

1461814

Hom.:

6230

Cov.:

AF XY:

0.0895

AC XY:

65118

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.0460

AC:

1539

AN:

33480

American (AMR)

AF:

0.0870

AC:

3890

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0623

AC:

1627

AN:

26134

East Asian (EAS)

AF:

0.0303

AC:

1201

AN:

39698

South Asian (SAS)

AF:

0.190

AC:

16416

AN:

86256

European-Finnish (FIN)

AF:

0.0902

AC:

4820

AN:

53408

Middle Eastern (MID)

AF:

0.0869

AC:

501

AN:

5768

European-Non Finnish (NFE)

AF:

0.0820

AC:

91201

AN:

1111960

Other (OTH)

AF:

0.0824

AC:

4979

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

7028

14056

21084

28112

35140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3440

6880

10320

13760

17200

<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:

0.0718

AC:

10917

AN:

152134

Hom.:

440

Cov.:

AF XY:

0.0742

AC XY:

5519

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0483

AC:

2005

AN:

41514

American (AMR)

AF:

0.0676

AC:

1033

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0602

AC:

209

AN:

3470

East Asian (EAS)

AF:

0.0297

AC:

154

AN:

5184

South Asian (SAS)

AF:

0.200

AC:

965

AN:

4816

European-Finnish (FIN)

AF:

0.0832

AC:

880

AN:

10580

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0808

AC:

5490

AN:

67986

Other (OTH)

AF:

0.0687

AC:

145

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

524

1048

1572

2096

2620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0781

Hom.:

1582

Bravo

AF:

0.0645

Asia WGS

AF:

0.124

AC:

431

AN:

3478

EpiCase

AF:

0.0770

EpiControl

AF:

0.0729

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jul 08, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

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

Thr343Thr in exon 8 of ENG: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 8.0% (691/8600) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs3739817). -

Oct 22, 2013

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:2

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cardiovascular phenotype

Benign:1

Aug 05, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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

Feb 04, 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

-0.53

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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