chr2-99440746-C-A

Variant names:

• chr2-99440746-C-A
• rs3792142
• NM_016316.4:c.504-1436G>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.504-1436G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,868 control chromosomes in the GnomAD database, including 14,030 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 0.43 (14030 hom., cov: 31)
• Consequence: REV1 NM_016316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 8 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 (AMR) allele frequency at 95% confidence interval = 0.563 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV1	NM_016316.4	MANE Select	c.504-1436G>T		intron	N/A	NP_057400.1
	REV1	NM_001321454.2		c.504-1436G>T		intron	N/A	NP_001308383.1
	REV1	NM_001037872.3		c.504-1436G>T		intron	N/A	NP_001032961.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV1	ENST00000258428.8	TSL:1 MANE Select	c.504-1436G>T		intron	N/A	ENSP00000258428.3
	REV1	ENST00000393445.7	TSL:1	c.504-1436G>T		intron	N/A	ENSP00000377091.3
	REV1	ENST00000879664.1		c.504-1436G>T		intron	N/A	ENSP00000549723.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64581 AN: 151750 Hom.: 14009 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.426 AC: 64636 AN: 151868 Hom.: 14030 Cov.: 31 AF XY: 0.426 AC XY: 31608 AN XY: 74202

African (AFR) AF: 0.380 AC: 15733 AN: 41408

American (AMR) AF: 0.573 AC: 8755 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1553 AN: 3462

East Asian (EAS) AF: 0.323 AC: 1667 AN: 5162

South Asian (SAS) AF: 0.293 AC: 1408 AN: 4808

European-Finnish (FIN) AF: 0.466 AC: 4905 AN: 10524

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29133 AN: 67930

Other (OTH) AF: 0.436 AC: 918 AN: 2104

Alfa AF: 0.265 Hom.: 597

Bravo AF: 0.440

Asia WGS AF: 0.322 AC: 1118 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	0.33
DANN	Benign	0.19
PhyloP100		-1.4
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: rs3792142; hg19: chr2-100057208;