rs5744724

Variant names:

• chr5-75599649-G-C
• rs5744724
• ENST00000514141.5:n.*2863G>C

Variant summary

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

The ENST00000514141.5(POLK):​n.*2863G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 152,076 control chromosomes in the GnomAD database, including 307 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 0.056 (307 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: POLK ENST00000514141.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• Publications: 8 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLK	NR_144315.3	n.4109G>C		non_coding_transcript_exon_variant	Exon 14 of 14
POLK	NR_170559.3	n.4098G>C		non_coding_transcript_exon_variant	Exon 14 of 14
POLK	NR_170560.3	n.4330G>C		non_coding_transcript_exon_variant	Exon 16 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000514141.5	n.*2863G>C		non_coding_transcript_exon_variant	Exon 13 of 13	1		ENSP00000423526.1
POLK	ENST00000241436.9	c.*1631G>C		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000241436.4
POLK	ENST00000514141.5	n.*2863G>C		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000423526.1

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8470 AN: 151958 Hom.: 305 Cov.: 32

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0881

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0537

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0558 AC: 8481 AN: 152076 Hom.: 307 Cov.: 32 AF XY: 0.0585 AC XY: 4349 AN XY: 74338

African (AFR) AF: 0.0322 AC: 1335 AN: 41510

American (AMR) AF: 0.0816 AC: 1246 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3468

East Asian (EAS) AF: 0.179 AC: 929 AN: 5180

South Asian (SAS) AF: 0.0328 AC: 158 AN: 4820

European-Finnish (FIN) AF: 0.0881 AC: 929 AN: 10548

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0541 AC: 3679 AN: 67964

Other (OTH) AF: 0.0560 AC: 118 AN: 2106

Alfa AF: 0.0544 Hom.: 33

Bravo AF: 0.0559

Asia WGS AF: 0.112 AC: 388 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.6
DANN	Benign	0.68
PhyloP100		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs5744724; hg19: chr5-74895474;