2-99445311-G-A

Variant names:

• chr2-99445311-G-A
• rs3792136
• NM_016316.4:c.351-2842C>T

Variant summary

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

The NM_016316.4(REV1):​c.351-2842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,168 control chromosomes in the GnomAD database, including 1,741 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 0.14 (1741 hom., cov: 32)
• Consequence: REV1 NM_016316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016316.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV1	NM_016316.4	MANE Select	c.351-2842C>T		intron	N/A	NP_057400.1
	REV1	NM_001321454.2		c.351-2842C>T		intron	N/A	NP_001308383.1
	REV1	NM_001037872.3		c.351-2842C>T		intron	N/A	NP_001032961.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV1	ENST00000258428.8	TSL:1 MANE Select	c.351-2842C>T		intron	N/A	ENSP00000258428.3
	REV1	ENST00000393445.7	TSL:1	c.351-2842C>T		intron	N/A	ENSP00000377091.3
	REV1	ENST00000413697.5	TSL:2	n.*298-2842C>T		intron	N/A	ENSP00000416274.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21876 AN: 152050 Hom.: 1741 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.195

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: 0.144 AC: 21884 AN: 152168 Hom.: 1741 Cov.: 32 AF XY: 0.147 AC XY: 10906 AN XY: 74396

African (AFR) AF: 0.111 AC: 4606 AN: 41508

American (AMR) AF: 0.222 AC: 3398 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3468

East Asian (EAS) AF: 0.247 AC: 1278 AN: 5176

South Asian (SAS) AF: 0.116 AC: 560 AN: 4826

European-Finnish (FIN) AF: 0.195 AC: 2071 AN: 10598

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9225 AN: 67994

Other (OTH) AF: 0.158 AC: 334 AN: 2116

Alfa AF: 0.133 Hom.: 216

Bravo AF: 0.149

Asia WGS AF: 0.173 AC: 601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.72
PhyloP100		-0.32
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: rs3792136; hg19: chr2-100061773; COSMIC: COSV51483179;