rs3730668

Variant names:

• chr18-54269477-G-C
• rs3730668
• ENST00000621167.1:n.552C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-54269477-G-C
• chr18-54269477-G-T

Variant summary

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

The ENST00000621167.1(ENSG00000277324):​n.552C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 1,481,126 control chromosomes in the GnomAD database, including 1 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 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000011 (1 hom.)
• Consequence: ENSG00000277324 ENST00000621167.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.834
• Publications: 19 publications found

Genes affected

ENSG00000277324 (HGNC:):

POLI (HGNC:9182): (DNA polymerase iota) The protein encoded by this gene is an error-prone DNA polymerase involved in DNA repair. The encoded protein promotes DNA synthesis across lesions in the template DNA, which other polymerases cannot do. The encoded polymerase inserts deoxynucleotides across lesions and then relies on DNA polymerase zeta to extend the nascent DNA strand to bypass the lesion. [provided by RefSeq, May 2017]

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 (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLI	NM_007195.3	c.-70G>C		upstream_gene_variant		ENST00000579534.6	NP_009126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLI	ENST00000579534.6	c.-70G>C		upstream_gene_variant		1	NM_007195.3	ENSP00000462664.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152068 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000113 AC: 15 AN: 1329058 Hom.: 1 Cov.: 32 AF XY: 0.00000458 AC XY: 3 AN XY: 655382

African (AFR) AF: 0.00 AC: 0 AN: 25478

American (AMR) AF: 0.00 AC: 0 AN: 20502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22452

East Asian (EAS) AF: 0.00 AC: 0 AN: 30074

South Asian (SAS) AF: 0.00 AC: 0 AN: 72104

European-Finnish (FIN) AF: 0.0000233 AC: 1 AN: 42862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4366

European-Non Finnish (NFE) AF: 0.0000133 AC: 14 AN: 1056184

Other (OTH) AF: 0.00 AC: 0 AN: 55036

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152068 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74274

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000750 Hom.: 587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.38
PhyloP100		0.83
PromoterAI		0.015	Neutral

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

Other links and lift over

dbSNP: rs3730668; hg19: chr18-51795847;