chr9-127824837-C-T

Position:

chr9-127824837-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001114753.3(ENG):c.954G>A(p.Pro318Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,594,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

ENG
NM_001114753.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.253

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 9-127824837-C-T is Benign according to our data. Variant chr9-127824837-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 528080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-127824837-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.253 with no splicing effect.

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENG	NM_001114753.3 linkuse as main transcript	c.954G>A	p.Pro318Pro	synonymous_variant	7/15	ENST00000373203.9	NP_001108225.1	P17813-1Q96CG0A0A024R878
ENG	NM_000118.4 linkuse as main transcript	c.954G>A	p.Pro318Pro	synonymous_variant	7/14		NP_000109.1	P17813-2Q5T9B9
ENG	NM_001278138.2 linkuse as main transcript	c.408G>A	p.Pro136Pro	synonymous_variant	7/15		NP_001265067.1	P17813Q96CG0F5GX88B7Z6Y5
ENG	NM_001406715.1 linkuse as main transcript	c.954G>A	p.Pro318Pro	synonymous_variant	7/8		NP_001393644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ENG	ENST00000373203.9 linkuse as main transcript	c.954G>A	p.Pro318Pro	synonymous_variant	7/15	1	NM_001114753.3	ENSP00000362299.4	P17813-1
ENG	ENST00000344849.4 linkuse as main transcript	c.954G>A	p.Pro318Pro	synonymous_variant	7/14	1		ENSP00000341917.3	P17813-2
ENG	ENST00000480266.6 linkuse as main transcript	c.408G>A	p.Pro136Pro	synonymous_variant	7/15	2		ENSP00000479015.1	F5GX88

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000809

AC:

AN:

234828

Hom.:

AF XY:

0.0000947

AC XY:

AN XY:

126664

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.0000317

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000233

AC:

336

AN:

1442458

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

160

AN XY:

715960

show subpopulations

Gnomad4 AFR exome

AF:

0.0000912

Gnomad4 AMR exome

AF:

0.0000962

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000275

Gnomad4 OTH exome

AF:

0.000370

GnomAD4 genome

AF:

0.000145

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000976

Hom.:

Bravo

AF:

0.000125

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Telangiectasia, hereditary hemorrhagic, type 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 28, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2021

- -

Cardiovascular phenotype

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2022

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.7

DANN

Benign

0.82

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