rs6542879

Variant names:

• chr2-99431138-A-G
• rs6542879
• NM_016316.4:c.1439-1190T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016316.4(REV1):​c.1439-1190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,020 control chromosomes in the GnomAD database, including 29,460 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 0.61 (29460 hom., cov: 32)
• Consequence: REV1 NM_016316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REV1	NM_016316.4	c.1439-1190T>C		intron_variant	Intron 8 of 22	ENST00000258428.8	NP_057400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REV1	ENST00000258428.8	c.1439-1190T>C		intron_variant	Intron 8 of 22	1	NM_016316.4	ENSP00000258428.3

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93235 AN: 151902 Hom.: 29404 Cov.: 32

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.572

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.614 AC: 93347 AN: 152020 Hom.: 29460 Cov.: 32 AF XY: 0.617 AC XY: 45806 AN XY: 74294

African (AFR) AF: 0.737 AC: 30574 AN: 41462

American (AMR) AF: 0.660 AC: 10078 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1734 AN: 3464

East Asian (EAS) AF: 0.359 AC: 1853 AN: 5162

South Asian (SAS) AF: 0.516 AC: 2484 AN: 4816

European-Finnish (FIN) AF: 0.670 AC: 7061 AN: 10544

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37677 AN: 67986

Other (OTH) AF: 0.570 AC: 1202 AN: 2110

Alfa AF: 0.595 Hom.: 3482

Bravo AF: 0.622

Asia WGS AF: 0.477 AC: 1657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.26
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6542879; hg19: chr2-100047600; COSMIC: COSV51491252; COSMIC: COSV51491252;