Genetic Variant ERV3-1:p.Ala277Thr (chr7-64992198-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001007253.4(ERV3-1):c.829G>A(p.Ala277Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 766,272 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

ERV3-1
NM_001007253.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.202

Variant links:

Genes affected

ERV3-1 (HGNC:3454): (endogenous retrovirus group 3 member 1, envelope) This gene contains sequence derived from endogenous retrovirus, and is therefore similar to multiple other loci in the genome. Transcripts at this locus encode a conserved protein with a predicted signal peptide and similarity to the Env polyprotein. This protein is overexpressed in colorectal and other cancers. [provided by RefSeq, Jan 2017]

ERV3-1 links:

ERV3-1-ZNF117 (HGNC:):

ERV3-1-ZNF117 links:

ZNF117 (HGNC:12897): (zinc finger protein 117) This gene encodes a protein containing multiple C2H2-type zinc finger motifs. Readthrough transcription occurs between this gene and the upstream endogenous retrovirus group 3 member 1 (ERV3-1) locus, and may result in additional transcript variants encoding the zinc finger protein. [provided by RefSeq, Jan 2017]

ZNF117 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00222376).

BP6

Variant 7-64992198-C-T is Benign according to our data. Variant chr7-64992198-C-T is described in ClinVar as [Benign]. Clinvar id is 709122.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERV3-1	NM_001007253.4 link	c.829G>A	p.Ala277Thr	missense_variant	Exon 2 of 2	ENST00000394323.3	NP_001007254.2	Q14264
ERV3-1	NM_001396062.1 link	c.829G>A	p.Ala277Thr	missense_variant	Exon 2 of 2		NP_001382991.1
ERV3-1-ZNF117	NM_001348050.2 link	c.-195-10082G>A		intron_variant	Intron 1 of 3		NP_001334979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERV3-1	ENST00000394323.3 link	c.829G>A	p.Ala277Thr	missense_variant	Exon 2 of 2	2	NM_001007253.4	ENSP00000391594.1		Q14264
ZNF117	ENST00000487644.1 link	n.145-10082G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00343

AC:

521

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000841

AC:

197

AN:

234322

Hom.:

AF XY:

0.000578

AC XY:

AN XY:

128064

show subpopulations

Gnomad AFR exome

AF:

0.0114

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000395

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000551

Gnomad OTH exome

AF:

0.000677

GnomAD4 exome

AF:

0.000606

AC:

372

AN:

614138

Hom.:

Cov.:

AF XY:

0.000486

AC XY:

163

AN XY:

335610

show subpopulations

Gnomad4 AFR exome

AF:

0.0105

Gnomad4 AMR exome

AF:

0.000252

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00347

Gnomad4 SAS exome

AF:

0.0000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000686

Gnomad4 OTH exome

AF:

0.000697

GnomAD4 genome

AF:

0.00343

AC:

522

AN:

152134

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

239

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0121

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000548

Hom.:

Bravo

AF:

0.00367

ESP6500AA

AF:

0.0121

AC:

ESP6500EA

AF:

0.000243

AC:

ExAC

AF:

0.00107

AC:

127

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 02, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.7

DANN

Benign

0.97

DEOGEN2

Benign

0.0015

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.48

PROVEAN

Benign

0.060

REVEL

Benign

0.015

Sift

Benign

0.050

Sift4G

Benign

0.30

Polyphen

0.10

Vest4

0.14

MVP

0.085

MPC

0.078

ClinPred

0.021

GERP RS

0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.050

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