5-75577212-A-G

Variant names:

• chr5-75577212-A-G
• rs5744655
• ENST00000241436.9:c.694+279A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.69).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLK	NM_001387111.3	c.694+279A>G		intron_variant	Intron 6 of 15		NP_001374040.1
POLK	NM_001395894.1	c.694+279A>G		intron_variant	Intron 7 of 16		NP_001382823.1
POLK	NM_001395897.1	c.733+279A>G		intron_variant	Intron 7 of 15		NP_001382826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000241436.9	c.694+279A>G		intron_variant	Intron 6 of 14	1		ENSP00000241436.4

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

African (AFR) AF: 0.00233 AC: 97 AN: 41582

American (AMR) AF: 0.00601 AC: 92 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3470

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5184

South Asian (SAS) AF: 0.0192 AC: 93 AN: 4832

European-Finnish (FIN) AF: 0.0281 AC: 298 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0124 AC: 844 AN: 68002

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

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
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

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: rs5744655; hg19: chr5-74873037;