rs5744545

Positions:

• chr5-75512592-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000241436.9(POLK):​c.-14+678G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0991 in 152,218 control chromosomes in the GnomAD database, including 890 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 0.099 (890 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: POLK ENST00000241436.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLK	NM_016218.6	c.-14+678G>A		intron_variant		ENST00000241436.9	NP_057302.1
POLK	NR_170560.3	n.24+678G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000241436.9	c.-14+678G>A		intron_variant		1	NM_016218.6	ENSP00000241436	P1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15082 AN: 152094 Hom.: 890 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0894

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0924

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0991 AC: 15087 AN: 152212 Hom.: 890 Cov.: 32 AF XY: 0.102 AC XY: 7591 AN XY: 74418

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.0928

Gnomad4 ASJ AF: 0.0894

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.109 Hom.: 1241

Bravo AF: 0.0905

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.75

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: rs5744545; hg19: chr5-74808417;