rs3087403

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-99442408-C-G
• chr2-99442408-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001321458.2(REV1):​c.-1183G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057017326).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV1	NM_016316.4	MANE Select	c.412G>C	p.Val138Leu	missense	Exon 5 of 23	NP_057400.1
	REV1	NM_001321458.2		c.-1183G>C		5_prime_UTR_premature_start_codon_gain	Exon 5 of 24	NP_001308387.1
	REV1	NM_001321459.2		c.-1358G>C		5_prime_UTR_premature_start_codon_gain	Exon 5 of 24	NP_001308388.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV1	ENST00000258428.8	TSL:1 MANE Select	c.412G>C	p.Val138Leu	missense	Exon 5 of 23	ENSP00000258428.3
	REV1	ENST00000393445.7	TSL:1	c.412G>C	p.Val138Leu	missense	Exon 5 of 23	ENSP00000377091.3
	REV1	ENST00000879664.1		c.412G>C	p.Val138Leu	missense	Exon 5 of 24	ENSP00000549723.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 29864

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.2
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.093
Sift	Benign	0.22	T
Sift4G	Benign	0.45	T
Polyphen		0.0010	B
Vest4		0.092
MutPred		0.42		Loss of catalytic residue at V138 (P = 0.0337)
MVP		0.27
MPC		0.89
ClinPred		0.055	T
GERP RS		1.8
Varity_R		0.032
gMVP		0.44
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;