8-47891114-T-C

Position:

• chr8-47891114-T-C

Variant summary

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

The NM_006904.7(PRKDC):​c.3848-634A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,906 control chromosomes in the GnomAD database, including 24,530 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 0.53 (24530 hom., cov: 31)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.3848-634A>G		intron_variant		ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.3848-634A>G		intron_variant			NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.3848-634A>G		intron_variant		1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.3848-634A>G		intron_variant		1		ENSP00000345182.4

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80606 AN: 151786 Hom.: 24484 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.531 AC: 80702 AN: 151906 Hom.: 24530 Cov.: 31 AF XY: 0.530 AC XY: 39345 AN XY: 74238

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.525

Alfa AF: 0.430 Hom.: 20085

Bravo AF: 0.551

Asia WGS AF: 0.529 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.35

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: rs10109984; hg19: chr8-48803675;