9-127815951-G-C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001114753.3(ENG):c.1844C>G(p.Ser615Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000563 in 1,599,460 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S615L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ENG
NM_001114753.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.10

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 9-127815951-G-C is Benign according to our data. Variant chr9-127815951-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 528060.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENG	NM_001114753.3 link	c.1844C>G	p.Ser615Trp	missense_variant	Exon 14 of 15	ENST00000373203.9	NP_001108225.1	P17813-1Q96CG0A0A024R878
ENG	NM_000118.4 link	c.1844C>G	p.Ser615Trp	missense_variant	Exon 14 of 14		NP_000109.1	P17813-2Q5T9B9
ENG	NM_001278138.2 link	c.1298C>G	p.Ser433Trp	missense_variant	Exon 14 of 15		NP_001265067.1	P17813Q96CG0F5GX88B7Z6Y5
LOC102723566	NR_136302.1 link	n.-115G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENG	ENST00000373203.9 link	c.1844C>G	p.Ser615Trp	missense_variant	Exon 14 of 15	1	NM_001114753.3	ENSP00000362299.4	P17813-1
ENG	ENST00000344849.4 link	c.1844C>G	p.Ser615Trp	missense_variant	Exon 14 of 14	1		ENSP00000341917.3	P17813-2
ENG	ENST00000480266.6 link	c.1298C>G	p.Ser433Trp	missense_variant	Exon 14 of 15	2		ENSP00000479015.1	F5GX88
ENSG00000225032	ENST00000439298.5 link	n.-115G>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000446

AC:

AN:

224358

Hom.:

AF XY:

0.00000824

AC XY:

AN XY:

121364

show subpopulations

Gnomad AFR exome

AF:

0.0000721

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000415

AC:

AN:

1447232

Hom.:

Cov.:

AF XY:

0.00000557

AC XY:

AN XY:

718596

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000491

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary hemorrhagic telangiectasia

Benign:1

Aug 16, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.90

D;T;.

Eigen

Benign

0.076

Eigen_PC

Benign

0.052

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.059

MetaRNN

Uncertain

0.53

D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

M;.;M

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.3

D;.;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

D;.;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.71

MutPred

0.42

Loss of disorder (P = 0.01);.;Loss of disorder (P = 0.01);

MVP

0.61

MPC

0.95

ClinPred

0.98

GERP RS

1.6

Varity_R

0.41

gMVP

0.85

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