rs4521758

Positions:

• chr8-47829009-C-T

Variant summary

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

The NM_006904.7(PRKDC):​c.8398-662G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,112 control chromosomes in the GnomAD database, including 8,339 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 0.26 (8339 hom., cov: 33)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975

Genes affected

PRKDC (HGNC:9413): (protein kinase, DNA-activated, catalytic subunit) This gene encodes the catalytic subunit of the DNA-dependent protein kinase (DNA-PK). It functions with the Ku70/Ku80 heterodimer protein in DNA double strand break repair and recombination. The protein encoded is a member of the PI3/PI4-kinase family.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKDC	NM_006904.7	c.8398-662G>A		intron_variant		ENST00000314191.7
PRKDC	NM_001081640.2	c.8398-662G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKDC	ENST00000314191.7	c.8398-662G>A		intron_variant		1	NM_006904.7	P1
PRKDC	ENST00000338368.7	c.8398-662G>A		intron_variant		1
PRKDC	ENST00000697603.1	c.1075-662G>A		intron_variant
PRKDC	ENST00000697608.1	n.917-662G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39660 AN: 151994 Hom.: 8323 Cov.: 33

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.261 AC: 39737 AN: 152112 Hom.: 8339 Cov.: 33 AF XY: 0.258 AC XY: 19202 AN XY: 74370

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0916

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.259

Alfa AF: 0.146 Hom.: 3281

Bravo AF: 0.294

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.84
DANN	Benign	0.49

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: rs4521758; hg19: chr8-48741570;