rs28369942

Variant names:

• chr2-99465099-A-AAAGTC
• rs28369942
• NM_016316.4:c.-10-115_-10-114insGACTT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -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 rank	MANE	Protein	UniProt
REV1	NM_016316.4	c.-10-115_-10-114insGACTT		intron_variant	Intron 1 of 22	ENST00000258428.8	NP_057400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REV1	ENST00000258428.8	c.-10-115_-10-114insGACTT		intron_variant	Intron 1 of 22	1	NM_016316.4	ENSP00000258428.3
REV1	ENST00000393445.7	c.-10-115_-10-114insGACTT		intron_variant	Intron 1 of 22	1		ENSP00000377091.3
REV1	ENST00000413697.5	n.-10-115_-10-114insGACTT		intron_variant	Intron 1 of 22	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

African (AFR) AF: 0.736 AC: 12163 AN: 16522

American (AMR) AF: 0.701 AC: 18081 AN: 25780

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 8551 AN: 18052

East Asian (EAS) AF: 0.340 AC: 10905 AN: 32100

South Asian (SAS) AF: 0.497 AC: 27895 AN: 56156

European-Finnish (FIN) AF: 0.645 AC: 30148 AN: 46720

Middle Eastern (MID) AF: 0.465 AC: 1825 AN: 3926

European-Non Finnish (NFE) AF: 0.542 AC: 253455 AN: 467616

Other (OTH) AF: 0.545 AC: 18443 AN: 33834

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

African (AFR) AF: 0.737 AC: 30425 AN: 41310

American (AMR) AF: 0.658 AC: 10042 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1729 AN: 3464

East Asian (EAS) AF: 0.360 AC: 1866 AN: 5178

South Asian (SAS) AF: 0.515 AC: 2477 AN: 4808

European-Finnish (FIN) AF: 0.668 AC: 7013 AN: 10494

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.553 AC: 37520 AN: 67828

Other (OTH) AF: 0.571 AC: 1202 AN: 2104

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs28369942; hg19: chr2-100081561;