rs41358947

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001114753.3(ENG):c.1794T>C(p.Gly598Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00575 in 1,610,468 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 44 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 110 hom. )

Consequence

ENG
NM_001114753.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -1.01

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:

ENSG00000225032 (HGNC:):

ENSG00000225032 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 9-127816001-A-G is Benign according to our data. Variant chr9-127816001-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 213203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-127816001-A-G is described in Lovd as [Benign]. Variant chr9-127816001-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2200/152302) while in subpopulation AFR AF= 0.0417 (1733/41554). AF 95% confidence interval is 0.0401. There are 44 homozygotes in gnomad4. There are 1084 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2200 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENG	NM_001114753.3 link	c.1794T>C	p.Gly598Gly	synonymous_variant	Exon 14 of 15	ENST00000373203.9	NP_001108225.1	P17813-1Q96CG0A0A024R878
ENG	NM_000118.4 link	c.1794T>C	p.Gly598Gly	synonymous_variant	Exon 14 of 14		NP_000109.1	P17813-2Q5T9B9
ENG	NM_001278138.2 link	c.1248T>C	p.Gly416Gly	synonymous_variant	Exon 14 of 15		NP_001265067.1	P17813Q96CG0F5GX88B7Z6Y5
LOC102723566	NR_136302.1 link	n.-65A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENG	ENST00000373203.9 link	c.1794T>C	p.Gly598Gly	synonymous_variant	Exon 14 of 15	1	NM_001114753.3	ENSP00000362299.4	P17813-1
ENG	ENST00000344849.4 link	c.1794T>C	p.Gly598Gly	synonymous_variant	Exon 14 of 14	1		ENSP00000341917.3	P17813-2
ENG	ENST00000480266.6 link	c.1248T>C	p.Gly416Gly	synonymous_variant	Exon 14 of 15	2		ENSP00000479015.1	F5GX88
ENSG00000225032	ENST00000439298.5 link	n.-65A>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2200

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0418

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00804

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0370

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00832

AC:

2019

AN:

242772

Hom.:

AF XY:

0.00885

AC XY:

1166

AN XY:

131712

show subpopulations

Gnomad AFR exome

AF:

0.0431

Gnomad AMR exome

AF:

0.00343

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.000388

Gnomad SAS exome

AF:

0.0347

Gnomad FIN exome

AF:

0.0000494

Gnomad NFE exome

AF:

0.00147

Gnomad OTH exome

AF:

0.00670

GnomAD4 exome

AF:

0.00485

AC:

7066

AN:

1458166

Hom.:

110

Cov.:

AF XY:

0.00562

AC XY:

4072

AN XY:

725040

show subpopulations

Gnomad4 AFR exome

AF:

0.0448

Gnomad4 AMR exome

AF:

0.00368

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0341

Gnomad4 FIN exome

AF:

0.000114

Gnomad4 NFE exome

AF:

0.00187

Gnomad4 OTH exome

AF:

0.00639

GnomAD4 genome

AF:

0.0144

AC:

2200

AN:

152302

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1084

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0417

Gnomad4 AMR

AF:

0.00803

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0366

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00187

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00689

Hom.:

Bravo

AF:

0.0162

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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

Gly598Gly in exon 14A of ENG: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 4.0% (178/4406) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs41358947). -

Dec 03, 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. -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

- -

Sep 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Feb 20, 2017

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

Jan 30, 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

-0.68

CADD

Benign

5.3

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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