5-75567216-T-C

Variant names:

• chr5-75567216-T-C
• rs3756558
• ENST00000241436.9:c.256-2124T>C

Variant summary

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

The ENST00000241436.9(POLK):​c.256-2124T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,236 control chromosomes in the GnomAD database, including 1,555 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 (1555 hom., cov: 32)
• Consequence: POLK ENST00000241436.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• Publications: 12 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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLK	NM_001387111.3	c.256-2124T>C		intron_variant	Intron 3 of 15		NP_001374040.1
POLK	NM_001395894.1	c.256-2124T>C		intron_variant	Intron 4 of 16		NP_001382823.1
POLK	NM_001395897.1	c.256-2124T>C		intron_variant	Intron 4 of 15		NP_001382826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000241436.9	c.256-2124T>C		intron_variant	Intron 3 of 14	1		ENSP00000241436.4

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20019 AN: 152118 Hom.: 1553 Cov.: 32

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.132 AC: 20021 AN: 152236 Hom.: 1555 Cov.: 32 AF XY: 0.136 AC XY: 10102 AN XY: 74432

African (AFR) AF: 0.0442 AC: 1838 AN: 41550

American (AMR) AF: 0.191 AC: 2924 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3464

East Asian (EAS) AF: 0.206 AC: 1068 AN: 5184

South Asian (SAS) AF: 0.152 AC: 736 AN: 4828

European-Finnish (FIN) AF: 0.198 AC: 2092 AN: 10588

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10435 AN: 68008

Other (OTH) AF: 0.117 AC: 248 AN: 2116

Alfa AF: 0.150 Hom.: 943

Bravo AF: 0.125

Asia WGS AF: 0.183 AC: 633 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		2.2
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: rs3756558; hg19: chr5-74863041;