rs28369942

Positions:

• chr2-99465099-A-AAAGTC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_016316.4(REV1):​c.-10-115_-10-114insGACTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 852,336 control chromosomes in the GnomAD database, including 138,195 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (29248 hom., cov: 0)
  • Exomes 𝑓: 0.54 (108947 hom.)
• Consequence: REV1 NM_016316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32

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 -8 ACMG points.

• 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/exons	MANE	Protein	UniProt
REV1	NM_016316.4	c.-10-115_-10-114insGACTT		intron_variant		ENST00000258428.8	NP_057400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REV1	ENST00000258428.8	c.-10-115_-10-114insGACTT		intron_variant		1	NM_016316.4	ENSP00000258428.3
REV1	ENST00000393445.7	c.-10-115_-10-114insGACTT		intron_variant		1		ENSP00000377091.3
REV1	ENST00000413697.5	n.-10-115_-10-114insGACTT		intron_variant		2		ENSP00000416274.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 92830 AN: 151516 Hom.: 29193 Cov.: 0

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.544 AC: 381466 AN: 700706 Hom.: 108947 AF XY: 0.540 AC XY: 197994 AN XY: 366518

Gnomad4 AFR exome AF: 0.736

Gnomad4 AMR exome AF: 0.701

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.497

Gnomad4 FIN exome AF: 0.645

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.545

GnomAD4 genome AF: 0.613 AC: 92939 AN: 151630 Hom.: 29248 Cov.: 0 AF XY: 0.615 AC XY: 45601 AN XY: 74088

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.571

Alfa AF: 0.593 Hom.: 2869

Bravo AF: 0.620

Asia WGS AF: 0.481 AC: 1668 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28369942; hg19: chr2-100081561;