rs5744655

Positions:

• chr5-75577212-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000241436.9(POLK):​c.694+279A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 152,308 control chromosomes in the GnomAD database, including 18 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 0.011 (18 hom., cov: 32)
• Consequence: POLK ENST00000241436.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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=-0.69).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0107 (1635/152308) while in subpopulation EAS AF= 0.0214 (111/5184). AF 95% confidence interval is 0.0182. There are 18 homozygotes in gnomad4. There are 872 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLK	NM_016218.6	c.694+279A>G		intron_variant		ENST00000241436.9	NP_057302.1
POLK	NR_170560.3	n.868+279A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000241436.9	c.694+279A>G		intron_variant		1	NM_016218.6	ENSP00000241436	P1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1637 AN: 152190 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0134

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

GnomAD4 genome AF: 0.0107 AC: 1635 AN: 152308 Hom.: 18 Cov.: 32 AF XY: 0.0117 AC XY: 872 AN XY: 74486

Gnomad4 AFR AF: 0.00233

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.0192

Gnomad4 FIN AF: 0.0281

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0122 Hom.: 1

Bravo AF: 0.00864

Asia WGS AF: 0.0210 AC: 74 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.88

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: rs5744655; hg19: chr5-74873037;