Variant 2-99402793-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016316.4(REV1):c.3392T>A(p.Leu1131His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,614,154 control chromosomes in the GnomAD database, including 53 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 0.0060 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0072 ( 47 hom. )

Consequence

REV1
NM_016316.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0950

Variant links:

Genes affected

REV1 (HGNC:14060): (REV1 DNA directed polymerase) This gene encodes a protein with similarity to the S. cerevisiae mutagenesis protein Rev1. The Rev1 proteins contain a BRCT domain, which is important in protein-protein interactions. A suggested role for the human Rev1-like protein is as a scaffold that recruits DNA polymerases involved in translesion synthesis (TLS) of damaged DNA. [provided by RefSeq, Mar 2016]

REV1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020717978).

BP6

Variant 2-99402793-A-T is Benign according to our data. Variant chr2-99402793-A-T is described in ClinVar as [Benign]. Clinvar id is 779405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REV1	NM_016316.4 linkuse as main transcript	c.3392T>A	p.Leu1131His	missense_variant	21/23	ENST00000258428.8	NP_057400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REV1	ENST00000258428.8 linkuse as main transcript	c.3392T>A	p.Leu1131His	missense_variant	21/23	1	NM_016316.4	ENSP00000258428	P4	Q9UBZ9-1

Frequencies

GnomAD3 genomes

AF:

0.00601

AC:

915

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00832

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00560

AC:

1406

AN:

251188

Hom.:

AF XY:

0.00562

AC XY:

763

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00342

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00317

Gnomad FIN exome

AF:

0.0141

Gnomad NFE exome

AF:

0.00726

Gnomad OTH exome

AF:

0.00703

GnomAD4 exome

AF:

0.00719

AC:

10508

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00710

AC XY:

5160

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00405

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00292

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.00810

Gnomad4 OTH exome

AF:

0.00682

GnomAD4 genome

AF:

0.00601

AC:

915

AN:

152360

Hom.:

Cov.:

AF XY:

0.00654

AC XY:

487

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00856

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.00832

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00692

Hom.:

Bravo

AF:

0.00527

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.00538

AC:

653

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00698

EpiControl

AF:

0.00694

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.5

DANN

Benign

0.87

DEOGEN2

Benign

0.040

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.18

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.088

Sift

Benign

0.55

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0010

B;B

Vest4

0.12

MVP

0.17

MPC

0.14

ClinPred

0.0091

GERP RS

-5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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