rs10077427

Variant names:

• chr5-75542076-A-G
• rs10077427
• ENST00000241436.9:c.-13-4934A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-75542076-A-G
• chr5-75542076-A-T

Variant summary

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

The ENST00000241436.9(POLK):​c.-13-4934A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,220 control chromosomes in the GnomAD database, including 1,370 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 0.13 (1370 hom., cov: 32)
• Consequence: POLK ENST00000241436.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 9 publications found

Genes affected

POLK (HGNC:9183): (DNA polymerase kappa) This gene encodes a member of the DNA polymerase type-Y family of proteins. The encoded protein is a specialized DNA polymerase that catalyzes translesion DNA synthesis, which allows DNA replication in the presence of DNA lesions. Human cell lines lacking a functional copy of this gene exhibit impaired genome integrity and enhanced susceptibility to oxidative damage. Mutations in this gene that impair enzyme activity may be associated with prostate cancer in human patients. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLK	NM_001387111.3	c.-13-4934A>G		intron_variant	Intron 1 of 15		NP_001374040.1
POLK	NM_001395894.1	c.-13-4934A>G		intron_variant	Intron 2 of 16		NP_001382823.1
POLK	NM_001395897.1	c.-13-4934A>G		intron_variant	Intron 2 of 15		NP_001382826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000241436.9	c.-13-4934A>G		intron_variant	Intron 1 of 14	1		ENSP00000241436.4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19604 AN: 152102 Hom.: 1370 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.122

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19611 AN: 152220 Hom.: 1370 Cov.: 32 AF XY: 0.132 AC XY: 9843 AN XY: 74402

African (AFR) AF: 0.107 AC: 4463 AN: 41546

American (AMR) AF: 0.113 AC: 1726 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1178 AN: 5174

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4816

European-Finnish (FIN) AF: 0.166 AC: 1758 AN: 10594

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8501 AN: 68008

Other (OTH) AF: 0.121 AC: 256 AN: 2114

Alfa AF: 0.0638 Hom.: 79

Bravo AF: 0.122

Asia WGS AF: 0.199 AC: 690 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.61
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs10077427; hg19: chr5-74837901;