rs3087400

chr2-99402968-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_016316.4(REV1):c.3305T>C(p.Leu1102Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,614,232 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.0029 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (3 hom.)
• Consequence: REV1 NM_016316.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.548

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040128827).
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REV1	NM_016316.4	c.3305T>C	p.Leu1102Pro	missense_variant	20/23	ENST00000258428.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REV1	ENST00000258428.8	c.3305T>C	p.Leu1102Pro	missense_variant	20/23	1	NM_016316.4	P4

Frequencies

GnomAD3 genomes AF: 0.00288 AC: 438 AN: 152230 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000732 AC: 184 AN: 251306 Hom.: 2 AF XY: 0.000523 AC XY: 71 AN XY: 135826

Gnomad AFR exome AF: 0.0104

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000264 AC: 386 AN: 1461884 Hom.: 3 Cov.: 32 AF XY: 0.000215 AC XY: 156 AN XY: 727246

Gnomad4 AFR exome AF: 0.00962

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.000546

GnomAD4 genome AF: 0.00289 AC: 441 AN: 152348 Hom.: 3 Cov.: 33 AF XY: 0.00262 AC XY: 195 AN XY: 74500

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000532 Hom.: 0

Bravo AF: 0.00327

ESP6500AA AF: 0.00953 AC: 42

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000939 AC: 114

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	14
Dann	Uncertain	0.99
Eigen	Benign	-0.073
Eigen_PC	Benign	-0.017
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.80	T;T
MetaRNN	Benign	0.0040	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.76	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.11
Sift	Benign	0.40	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.0070	B;P
Vest4		0.12
MVP		0.29
MPC		0.17
ClinPred		0.054	T
GERP RS		4.8
Varity_R		0.19
gMVP		0.53

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

Other links and lift over

dbSNP: rs3087400; hg19: chr2-100019431;