Variant chr19-53050086-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001191055.2(ERVV-2):c.835C>G(p.Pro279Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.013 ( 25 hom., cov: 21)

Exomes 𝑓: 0.0087 ( 1258 hom. )

Failed GnomAD Quality Control

Consequence

ERVV-2
NM_001191055.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.637

Variant links:

Genes affected

ERVV-2 (HGNC:39051): (endogenous retrovirus group V member 2, envelope) Many different human endogenous retrovirus (HERV) families are expressed in normal placental tissue at high levels, suggesting that HERVs are functionally important in reproduction. This gene is part of an HERV provirus on human chromosome 19 that has inactivating mutations in the gag and pol genes. This envelope glycoprotein gene appears to have been selectively preserved. The gene's protein product is expressed in the placenta and acts as a syncytin in Old World monkeys, but has lost the fusogenic activity in humans and other primate lineages. [provided by RefSeq, Jun 2015]

ERVV-2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006170988).

BP6

Variant 19-53050086-C-G is Benign according to our data. Variant chr19-53050086-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3090403.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERVV-2	NM_001191055.2 link	c.835C>G	p.Pro279Ala	missense_variant	Exon 2 of 2	ENST00000601417.3	NP_001177984.1	B6SEH9M9QSX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERVV-2	ENST00000601417.3 link	c.835C>G	p.Pro279Ala	missense_variant	Exon 2 of 2	4	NM_001191055.2	ENSP00000472919.1		B6SEH9

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1686

AN:

134170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00375

Gnomad AMI

AF:

0.0125

Gnomad AMR

AF:

0.00892

Gnomad ASJ

AF:

0.0142

Gnomad EAS

AF:

0.0305

Gnomad SAS

AF:

0.0366

Gnomad FIN

AF:

0.00884

Gnomad MID

AF:

0.0393

Gnomad NFE

AF:

0.0161

Gnomad OTH

AF:

0.0126

GnomAD3 exomes

AF:

0.00710

AC:

893

AN:

125702

Hom.:

160

AF XY:

0.00705

AC XY:

482

AN XY:

68346

show subpopulations

Gnomad AFR exome

AF:

0.00353

Gnomad AMR exome

AF:

0.00640

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.0121

Gnomad SAS exome

AF:

0.00988

Gnomad FIN exome

AF:

0.00255

Gnomad NFE exome

AF:

0.00698

Gnomad OTH exome

AF:

0.00909

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00873

AC:

11322

AN:

1296826

Hom.:

1258

Cov.:

AF XY:

0.00948

AC XY:

6063

AN XY:

639778

show subpopulations

Gnomad4 AFR exome

AF:

0.00389

Gnomad4 AMR exome

AF:

0.00924

Gnomad4 ASJ exome

AF:

0.0133

Gnomad4 EAS exome

AF:

0.0251

Gnomad4 SAS exome

AF:

0.0196

Gnomad4 FIN exome

AF:

0.0167

Gnomad4 NFE exome

AF:

0.00696

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0125

AC:

1679

AN:

134266

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

783

AN XY:

65498

show subpopulations

Gnomad4 AFR

AF:

0.00373

Gnomad4 AMR

AF:

0.00883

Gnomad4 ASJ

AF:

0.0142

Gnomad4 EAS

AF:

0.0301

Gnomad4 SAS

AF:

0.0365

Gnomad4 FIN

AF:

0.00884

Gnomad4 NFE

AF:

0.0161

Gnomad4 OTH

AF:

0.0124

Alfa

AF:

0.00828

Hom.:

ExAC

AF:

0.00286

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 16, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.31

DANN

Benign

0.53

DEOGEN2

Benign

0.0058

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.42

M_CAP

Benign

0.0090

MetaRNN

Benign

0.0062

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.36

Sift4G

Pathogenic

0.0

Vest4

0.10

MVP

0.14

GERP RS

0.42

Varity_R

0.032

gMVP

0.20

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