rs11545664

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001114753.3(ENG):c.207G>A(p.Leu69Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 1,613,932 control chromosomes in the GnomAD database, including 9,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1782 hom., cov: 31)

Exomes 𝑓: 0.094 ( 7269 hom. )

Consequence

ENG
NM_001114753.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.15

Publications

26 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 9-127843106-C-T is Benign according to our data. Variant chr9-127843106-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENG	NM_001114753.3 link	c.207G>A	p.Leu69Leu	synonymous_variant	Exon 2 of 15	ENST00000373203.9	NP_001108225.1	P17813-1Q96CG0A0A024R878
ENG	NM_000118.4 link	c.207G>A	p.Leu69Leu	synonymous_variant	Exon 2 of 14		NP_000109.1	P17813-2Q5T9B9
ENG	NM_001406715.1 link	c.207G>A	p.Leu69Leu	synonymous_variant	Exon 2 of 8		NP_001393644.1
ENG	NM_001278138.2 link	c.-340G>A		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.207G>A	p.Leu69Leu	synonymous_variant	Exon 2 of 15	1	NM_001114753.3	ENSP00000362299.4		P17813-1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20675

AN:

152100

Hom.:

1781

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.0520

Gnomad SAS

AF:

0.0476

Gnomad FIN

AF:

0.0625

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.133

GnomAD2 exomes

AF:

0.0928

AC:

23319

AN:

251284

AF XY:

0.0900

show subpopulations

Gnomad AFR exome

AF:

0.242

Gnomad AMR exome

AF:

0.0631

Gnomad ASJ exome

AF:

0.0961

Gnomad EAS exome

AF:

0.0456

Gnomad FIN exome

AF:

0.0690

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0936

AC:

136802

AN:

1461714

Hom.:

7269

Cov.:

AF XY:

0.0924

AC XY:

67212

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.255

AC:

8537

AN:

33470

American (AMR)

AF:

0.0661

AC:

2955

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

2633

AN:

26132

East Asian (EAS)

AF:

0.0451

AC:

1789

AN:

39700

South Asian (SAS)

AF:

0.0528

AC:

4556

AN:

86248

European-Finnish (FIN)

AF:

0.0721

AC:

3850

AN:

53386

Middle Eastern (MID)

AF:

0.167

AC:

959

AN:

5744

European-Non Finnish (NFE)

AF:

0.0949

AC:

105545

AN:

1111938

Other (OTH)

AF:

0.0990

AC:

5978

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

8095

16190

24285

32380

40475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3774

7548

11322

15096

18870

<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:

0.136

AC:

20687

AN:

152218

Hom.:

1782

Cov.:

AF XY:

0.132

AC XY:

9808

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.239

AC:

9905

AN:

41518

American (AMR)

AF:

0.107

AC:

1635

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

352

AN:

3472

East Asian (EAS)

AF:

0.0517

AC:

268

AN:

5184

South Asian (SAS)

AF:

0.0476

AC:

230

AN:

4828

European-Finnish (FIN)

AF:

0.0625

AC:

663

AN:

10614

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

7000

AN:

67994

Other (OTH)

AF:

0.131

AC:

276

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

896

1793

2689

3586

4482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.126

Hom.:

1432

Bravo

AF:

0.143

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

EpiCase

AF:

0.104

EpiControl

AF:

0.105

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

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leu69Leu 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 25.2% (1109/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs16930129). -

Feb 06, 2014

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Telangiectasia, hereditary hemorrhagic, type 1

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: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

Dec 10, 2014

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

-0.38

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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