chr2-99430321-C-T

Position:

• chr2-99430321-C-T

Variant summary

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

The NM_016316.4(REV1):​c.1439-373G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,716 control chromosomes in the GnomAD database, including 5,863 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 0.28 (5863 hom., cov: 31)
• Consequence: REV1 NM_016316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REV1	NM_016316.4	c.1439-373G>A		intron_variant		ENST00000258428.8	NP_057400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REV1	ENST00000258428.8	c.1439-373G>A		intron_variant		1	NM_016316.4	ENSP00000258428	P4

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41740 AN: 151598 Hom.: 5855 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.0729

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.275 AC: 41774 AN: 151716 Hom.: 5863 Cov.: 31 AF XY: 0.274 AC XY: 20271 AN XY: 74110

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.0731

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.275

Alfa AF: 0.282 Hom.: 1028

Bravo AF: 0.284

Asia WGS AF: 0.136 AC: 472 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.1
DANN	Benign	0.54

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: rs4341989; hg19: chr2-100046783;