2-99442408-C-T

Variant names:

• chr2-99442408-C-T
• rs3087403
• NM_016316.4:c.412G>A

Variant summary

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

The NM_001321458.2(REV1):​c.-1183G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,612,946 control chromosomes in the GnomAD database, including 61,510 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 (5878 hom., cov: 31)
  • Exomes 𝑓: 0.27 (55632 hom.)
• Consequence: REV1 NM_001321458.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 35 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 (MetaRNN=0.002084881).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321458.2. 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.412G>A	p.Val138Met	missense	Exon 5 of 23	NP_057400.1	Q9UBZ9-1
	REV1	NM_001321458.2		c.-1183G>A		5_prime_UTR_premature_start_codon_gain	Exon 5 of 24	NP_001308387.1
	REV1	NM_001321459.2		c.-1358G>A		5_prime_UTR_premature_start_codon_gain	Exon 5 of 24	NP_001308388.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV1	ENST00000258428.8	TSL:1 MANE Select	c.412G>A	p.Val138Met	missense	Exon 5 of 23	ENSP00000258428.3	Q9UBZ9-1
	REV1	ENST00000393445.7	TSL:1	c.412G>A	p.Val138Met	missense	Exon 5 of 23	ENSP00000377091.3	Q9UBZ9-2
	REV1	ENST00000879664.1		c.412G>A	p.Val138Met	missense	Exon 5 of 24	ENSP00000549723.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41821 AN: 151842 Hom.: 5864 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.270

GnomAD2 exomes AF: 0.275 AC: 69111 AN: 251226 AF XY: 0.267

Gnomad AFR exome AF: 0.283

Gnomad AMR exome AF: 0.432

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.0665

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.270 AC: 394779 AN: 1460986 Hom.: 55632 Cov.: 36 AF XY: 0.267 AC XY: 194364 AN XY: 726804

African (AFR) AF: 0.284 AC: 9510 AN: 33448

American (AMR) AF: 0.419 AC: 18718 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 8733 AN: 26114

East Asian (EAS) AF: 0.0674 AC: 2674 AN: 39698

South Asian (SAS) AF: 0.186 AC: 16032 AN: 86206

European-Finnish (FIN) AF: 0.255 AC: 13630 AN: 53386

Middle Eastern (MID) AF: 0.315 AC: 1814 AN: 5766

European-Non Finnish (NFE) AF: 0.277 AC: 307682 AN: 1111342

Other (OTH) AF: 0.265 AC: 15986 AN: 60344

GnomAD4 genome AF: 0.276 AC: 41872 AN: 151960 Hom.: 5878 Cov.: 31 AF XY: 0.274 AC XY: 20321 AN XY: 74286

African (AFR) AF: 0.281 AC: 11657 AN: 41426

American (AMR) AF: 0.344 AC: 5251 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1220 AN: 3470

East Asian (EAS) AF: 0.0683 AC: 353 AN: 5166

South Asian (SAS) AF: 0.172 AC: 832 AN: 4826

European-Finnish (FIN) AF: 0.262 AC: 2765 AN: 10554

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18914 AN: 67962

Other (OTH) AF: 0.268 AC: 562 AN: 2100

Alfa AF: 0.279 Hom.: 29864

Bravo AF: 0.286

TwinsUK AF: 0.285 AC: 1058

ALSPAC AF: 0.276 AC: 1063

ESP6500AA AF: 0.283 AC: 1246

ESP6500EA AF: 0.279 AC: 2396

ExAC AF: 0.268 AC: 32476

Asia WGS AF: 0.146 AC: 508 AN: 3478

EpiCase AF: 0.283

EpiControl AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.2
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.096
Sift	Benign	0.11	T
Sift4G	Benign	0.12	T
Polyphen		0.019	B
Vest4		0.073
MPC		0.96
ClinPred		0.0034	T
GERP RS		1.8
Varity_R		0.023
gMVP		0.44
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3087403; hg19: chr2-100058870; COSMIC: COSV51481954; COSMIC: COSV51481954;