rs115450389

Positions:

chr9-127818354-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001114753.3(ENG):c.1452C>T(p.Ser484=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000899 in 1,613,796 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 3 hom. )

Consequence

ENG
NM_001114753.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.29

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 9-127818354-G-A is Benign according to our data. Variant chr9-127818354-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-127818354-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00295 (449/152334) while in subpopulation AFR AF= 0.00873 (363/41562). AF 95% confidence interval is 0.00799. There are 3 homozygotes in gnomad4. There are 205 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 449 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ENG	NM_001114753.3 linkuse as main transcript	c.1452C>T	p.Ser484=	synonymous_variant	12/15	ENST00000373203.9	NP_001108225.1
LOC102723566	NR_136302.1 linkuse as main transcript	n.1421G>A		non_coding_transcript_exon_variant	3/6
ENG	NM_000118.4 linkuse as main transcript	c.1452C>T	p.Ser484=	synonymous_variant	12/14		NP_000109.1
ENG	NM_001278138.2 linkuse as main transcript	c.906C>T	p.Ser302=	synonymous_variant	12/15		NP_001265067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENG	ENST00000373203.9 linkuse as main transcript	c.1452C>T	p.Ser484=	synonymous_variant	12/15	1	NM_001114753.3	ENSP00000362299	P2	P17813-1
	ENST00000439298.5 linkuse as main transcript	n.1421G>A		non_coding_transcript_exon_variant	3/6	2

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

446

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00866

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00112

AC:

279

AN:

248912

Hom.:

AF XY:

0.000890

AC XY:

120

AN XY:

134806

show subpopulations

Gnomad AFR exome

AF:

0.00896

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000420

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.000686

AC:

1002

AN:

1461462

Hom.:

Cov.:

AF XY:

0.000640

AC XY:

465

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.00821

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000463

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

AF:

0.00295

AC:

449

AN:

152334

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00873

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.00319

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000533

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Telangiectasia, hereditary hemorrhagic, type 1

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 13, 2019	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	ENG: BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 11, 2018	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2016

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

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.2

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: -16

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