rs16930129

Positions:

chr9-127843106-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 137208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-127843106-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ENG	NM_001114753.3 linkuse as main transcript	c.207G>A	p.Leu69Leu	synonymous_variant	2/15	ENST00000373203.9	NP_001108225.1	P17813-1Q96CG0A0A024R878
ENG	NM_000118.4 linkuse as main transcript	c.207G>A	p.Leu69Leu	synonymous_variant	2/14		NP_000109.1	P17813-2Q5T9B9
ENG	NM_001406715.1 linkuse as main transcript	c.207G>A	p.Leu69Leu	synonymous_variant	2/8		NP_001393644.1
ENG	NM_001278138.2 linkuse as main transcript	c.-340G>A		5_prime_UTR_variant	2/15		NP_001265067.1	P17813Q96CG0F5GX88B7Z6Y5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ENG	ENST00000373203.9 linkuse as main transcript	c.207G>A	p.Leu69Leu	synonymous_variant	2/15	1	NM_001114753.3	ENSP00000362299.4	P17813-1
ENG	ENST00000344849.4 linkuse as main transcript	c.207G>A	p.Leu69Leu	synonymous_variant	2/14	1		ENSP00000341917.3	P17813-2
ENG	ENST00000480266.6 linkuse as main transcript	c.-340G>A		5_prime_UTR_variant	2/15	2		ENSP00000479015.1	F5GX88

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

GnomAD3 exomes

AF:

0.0928

AC:

23319

AN:

251284

Hom.:

1412

AF XY:

0.0900

AC XY:

12218

AN XY:

135826

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 SAS exome

AF:

0.0517

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

Gnomad4 AFR exome

AF:

0.255

Gnomad4 AMR exome

AF:

0.0661

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.0451

Gnomad4 SAS exome

AF:

0.0528

Gnomad4 FIN exome

AF:

0.0721

Gnomad4 NFE exome

AF:

0.0949

Gnomad4 OTH exome

AF:

0.0990

GnomAD4 genome

AF:

0.136

AC:

20687

AN:

152218

Hom.:

1782

Cov.:

AF XY:

0.132

AC XY:

9808

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.239

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.0517

Gnomad4 SAS

AF:

0.0476

Gnomad4 FIN

AF:

0.0625

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.106

Hom.:

513

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	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). -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 08, 2021	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 06, 2014	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

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 28, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2014

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over