rs10077427

chr5-75542076-A-Gchr5-75542076-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
POLK	NM_016218.6	c.-13-4934A>G		intron_variant		ENST00000241436.9
POLK	NR_170560.3	n.162-4934A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLK	ENST00000241436.9	c.-13-4934A>G		intron_variant		1	NM_016218.6	P1

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

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.121

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10077427; hg19: chr5-74837901;