Variant 2-99442408-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001321458.2(REV1):c.-1183G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,612,946 control chromosomes in the GnomAD database, including 61,510 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 5878 hom., cov: 31)

Exomes 𝑓: 0.27 ( 55632 hom. )

Consequence

REV1
NM_001321458.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

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:

REV1 (HGNC:):

REV1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002084881).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.336 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.412G>A	p.Val138Met	missense_variant	5/23	ENST00000258428.8	NP_057400.1	Q9UBZ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REV1	ENST00000258428.8 linkuse as main transcript	c.412G>A	p.Val138Met	missense_variant	5/23	1	NM_016316.4	ENSP00000258428.3		Q9UBZ9-1

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41821

AN:

151842

Hom.:

5864

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.352

Gnomad EAS

AF:

0.0684

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.328

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.275

AC:

69111

AN:

251226

Hom.:

10521

AF XY:

0.267

AC XY:

36289

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.283

Gnomad AMR exome

AF:

0.432

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.0665

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.258

Gnomad NFE exome

AF:

0.282

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.270

AC:

394779

AN:

1460986

Hom.:

55632

Cov.:

AF XY:

0.267

AC XY:

194364

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.0674

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.255

Gnomad4 NFE exome

AF:

0.277

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.276

AC:

41872

AN:

151960

Hom.:

5878

Cov.:

AF XY:

0.274

AC XY:

20321

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.281

Gnomad4 AMR

AF:

0.344

Gnomad4 ASJ

AF:

0.352

Gnomad4 EAS

AF:

0.0683

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.278

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.280

Hom.:

15788

Bravo

AF:

0.286

TwinsUK

AF:

0.285

AC:

1058

ALSPAC

AF:

0.276

AC:

1063

ESP6500AA

AF:

0.283

AC:

1246

ESP6500EA

AF:

0.279

AC:

2396

ExAC

AF:

0.268

AC:

32476

Asia WGS

AF:

0.146

AC:

508

AN:

3478

EpiCase

AF:

0.283

EpiControl

AF:

0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.048

.;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.66

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.96

N;N

REVEL

Benign

0.096

Sift

Benign

0.11

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.019

B;B

Vest4

0.073

MPC

0.96

ClinPred

0.0034

GERP RS

1.8

Varity_R

0.023

gMVP

0.44

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over