rs7003908

Positions:

• chr8-47858141-C-A
• chr8-47858141-C-G
• chr8-47858141-C-T

Variant summary

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

The ENST00000314191.7(PRKDC):​c.6465+375G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 151,836 control chromosomes in the GnomAD database, including 33,597 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 0.66 (33597 hom., cov: 30)
• Consequence: PRKDC ENST00000314191.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.6465+375G>T		intron_variant		ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.6465+375G>T		intron_variant			NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.6465+375G>T		intron_variant		1	NM_006904.7	ENSP00000313420	P1
PRKDC	ENST00000338368.7	c.6465+375G>T		intron_variant		1		ENSP00000345182
PRKDC	ENST00000697609.1	n.626+375G>T		intron_variant, non_coding_transcript_variant
PRKDC	ENST00000697610.1	n.266+375G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100697 AN: 151718 Hom.: 33569 Cov.: 30

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.664 AC: 100780 AN: 151836 Hom.: 33597 Cov.: 30 AF XY: 0.665 AC XY: 49352 AN XY: 74202

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.638

Alfa AF: 0.639 Hom.: 37875

Bravo AF: 0.669

Asia WGS AF: 0.654 AC: 2273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.064
DANN	Benign	0.47

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: rs7003908; hg19: chr8-48770702;