rs9941566

Positions:

• chr2-99423437-G-A
• chr2-99423437-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016316.4(REV1):​c.1676+715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,032 control chromosomes in the GnomAD database, including 1,794 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 0.15 (1794 hom., cov: 32)
• Consequence: REV1 NM_016316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REV1	NM_016316.4	c.1676+715C>T		intron_variant		ENST00000258428.8	NP_057400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REV1	ENST00000258428.8	c.1676+715C>T		intron_variant		1	NM_016316.4	ENSP00000258428.3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22304 AN: 151914 Hom.: 1793 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.147 AC: 22314 AN: 152032 Hom.: 1794 Cov.: 32 AF XY: 0.149 AC XY: 11108 AN XY: 74318

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.157

Alfa AF: 0.144 Hom.: 267

Bravo AF: 0.152

Asia WGS AF: 0.176 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.64

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: rs9941566; hg19: chr2-100039899;