Genetic Variant ERVV-2:p.Pro251Ala (chr19-53050002-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001191055.2(ERVV-2):c.751C>G(p.Pro251Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,499,472 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000062 ( 1 hom. )

Consequence

ERVV-2
NM_001191055.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.305

Publications

1 publications found

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:

ZNF702P (HGNC:):

ZNF702P links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.053248346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001191055.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERVV-2	NM_001191055.2	MANE Select	c.751C>G	p.Pro251Ala	missense	Exon 2 of 2	NP_001177984.1	B6SEH9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERVV-2	ENST00000601417.3	TSL:4 MANE Select	c.751C>G	p.Pro251Ala	missense	Exon 2 of 2	ENSP00000472919.1	B6SEH9
	ZNF702P	ENST00000816847.1		n.382+6564G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000594

AC:

AN:

134690

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00147

Gnomad SAS

AF:

0.000259

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000154

AC:

AN:

130212

AF XY:

0.000141

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00172

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000623

AC:

AN:

1364684

Hom.:

Cov.:

AF XY:

0.0000667

AC XY:

AN XY:

674190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31176

American (AMR)

AF:

0.00

AC:

AN:

35350

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25044

East Asian (EAS)

AF:

0.00196

AC:

AN:

35664

South Asian (SAS)

AF:

0.000115

AC:

AN:

78584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33840

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

9.41e-7

AC:

AN:

1062202

Other (OTH)

AF:

0.0000699

AC:

AN:

57186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000594

AC:

AN:

134788

Hom.:

Cov.:

AF XY:

0.0000614

AC XY:

AN XY:

65186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

35418

American (AMR)

AF:

0.00

AC:

AN:

12740

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3246

East Asian (EAS)

AF:

0.00147

AC:

AN:

4768

South Asian (SAS)

AF:

0.000259

AC:

AN:

3854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62632

Other (OTH)

AF:

0.00

AC:

AN:

1848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000718

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.55

M_CAP

Benign

0.014

MetaRNN

Benign

0.053

MutationAssessor

Uncertain

2.3

PhyloP100

0.30

PrimateAI

Benign

0.38

Sift4G

Pathogenic

0.0

Vest4

0.23

MVP

0.38

GERP RS

0.42

Varity_R

0.061

gMVP

0.65

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over