rs1018119

Variant names:

• chr5-75590559-G-A
• rs1018119
• ENST00000241436.9:c.1356+119G>A

Variant summary

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

The NM_001387111.3(POLK):​c.1398+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 663,376 control chromosomes in the GnomAD database, including 3,105 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 0.078 (555 hom., cov: 32)
  • Exomes 𝑓: 0.092 (2550 hom.)
• Consequence: POLK NM_001387111.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLK	NM_001387111.3	c.1398+119G>A		intron_variant	Intron 12 of 15		NP_001374040.1
POLK	NM_001395894.1	c.1398+119G>A		intron_variant	Intron 13 of 16		NP_001382823.1
POLK	NM_001395897.1	c.1395+119G>A		intron_variant	Intron 12 of 15		NP_001382826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000241436.9	c.1356+119G>A		intron_variant	Intron 11 of 14	1		ENSP00000241436.4

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11879 AN: 152084 Hom.: 551 Cov.: 32

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0703

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.0888

GnomAD4 exome AF: 0.0921 AC: 47076 AN: 511174 Hom.: 2550 Cov.: 6 AF XY: 0.0971 AC XY: 26645 AN XY: 274412

Gnomad4 AFR exome AF: 0.0601

Gnomad4 AMR exome AF: 0.0502

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.0766

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.0663

Gnomad4 NFE exome AF: 0.0853

Gnomad4 OTH exome AF: 0.0907

GnomAD4 genome AF: 0.0782 AC: 11895 AN: 152202 Hom.: 555 Cov.: 32 AF XY: 0.0797 AC XY: 5932 AN XY: 74400

Gnomad4 AFR AF: 0.0604

Gnomad4 AMR AF: 0.0683

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0701

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.0835

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.0809 Hom.: 107

Bravo AF: 0.0748

Asia WGS AF: 0.118 AC: 408 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.54

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: rs1018119; hg19: chr5-74886384;