Variant rs3087386 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016316.4(REV1):c.770T>C(p.Phe257Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,613,544 control chromosomes in the GnomAD database, including 258,604 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.61 ( 28676 hom., cov: 32)

Exomes 𝑓: 0.56 ( 229928 hom. )

Consequence

REV1
NM_016316.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.902

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0208001E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REV1	NM_016316.4 linkuse as main transcript	c.770T>C	p.Phe257Ser	missense_variant	6/23	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.770T>C	p.Phe257Ser	missense_variant	6/23	1	NM_016316.4	ENSP00000258428	P4	Q9UBZ9-1

Frequencies

GnomAD3 genomes

AF:

0.607

AC:

92186

AN:

151900

Hom.:

28640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.712

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.656

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.671

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.567

GnomAD3 exomes

AF:

0.578

AC:

144782

AN:

250650

Hom.:

43058

AF XY:

0.565

AC XY:

76554

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.717

Gnomad AMR exome

AF:

0.731

Gnomad ASJ exome

AF:

0.480

Gnomad EAS exome

AF:

0.358

Gnomad SAS exome

AF:

0.508

Gnomad FIN exome

AF:

0.655

Gnomad NFE exome

AF:

0.560

Gnomad OTH exome

AF:

0.561

GnomAD4 exome

AF:

0.557

AC:

814556

AN:

1461526

Hom.:

229928

Cov.:

AF XY:

0.554

AC XY:

402687

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.713

Gnomad4 AMR exome

AF:

0.720

Gnomad4 ASJ exome

AF:

0.483

Gnomad4 EAS exome

AF:

0.345

Gnomad4 SAS exome

AF:

0.506

Gnomad4 FIN exome

AF:

0.647

Gnomad4 NFE exome

AF:

0.556

Gnomad4 OTH exome

AF:

0.547

GnomAD4 genome

AF:

0.607

AC:

92271

AN:

152018

Hom.:

28676

Cov.:

AF XY:

0.610

AC XY:

45304

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.712

Gnomad4 AMR

AF:

0.657

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.361

Gnomad4 SAS

AF:

0.515

Gnomad4 FIN

AF:

0.671

Gnomad4 NFE

AF:

0.554

Gnomad4 OTH

AF:

0.564

Alfa

AF:

0.555

Hom.:

47988

Bravo

AF:

0.614

TwinsUK

AF:

0.560

AC:

2078

ALSPAC

AF:

0.544

AC:

2096

ESP6500AA

AF:

0.707

AC:

3115

ESP6500EA

AF:

0.547

AC:

4708

ExAC

AF:

0.574

AC:

69739

Asia WGS

AF:

0.479

AC:

1663

AN:

3478

EpiCase

AF:

0.546

EpiControl

AF:

0.561

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.47

DANN

Benign

0.48

DEOGEN2

Benign

0.010

.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.033

T;T

MetaRNN

Benign

0.0000010

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.0

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

1.4

N;N

REVEL

Benign

0.029

Sift

Benign

0.47

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0

B;B

Vest4

0.054

MPC

0.19

ClinPred

0.012

GERP RS

-0.027

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over