rs7003908

Variant names:

• chr8-47858141-C-A
• rs7003908
• NM_006904.7:c.6465+375G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_006904.7(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 NM_006904.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839
• Publications: 63 publications found

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]

PRKDC Gene-Disease associations (from GenCC):

• severe combined immunodeficiency due to DNA-PKcs deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.6465+375G>T		intron_variant	Intron 48 of 85	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.6465+375G>T		intron_variant	Intron 48 of 84		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.6465+375G>T		intron_variant	Intron 48 of 85	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.6465+375G>T		intron_variant	Intron 48 of 84	1		ENSP00000345182.4
PRKDC	ENST00000697609.1	n.626+375G>T		intron_variant	Intron 2 of 3
PRKDC	ENST00000697610.1	n.266+375G>T		intron_variant	Intron 3 of 3

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

African (AFR) AF: 0.683 AC: 28285 AN: 41404

American (AMR) AF: 0.721 AC: 11017 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3462

East Asian (EAS) AF: 0.777 AC: 4003 AN: 5152

South Asian (SAS) AF: 0.559 AC: 2693 AN: 4820

European-Finnish (FIN) AF: 0.654 AC: 6870 AN: 10504

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.652 AC: 44287 AN: 67912

Other (OTH) AF: 0.638 AC: 1342 AN: 2104

Alfa AF: 0.646 Hom.: 55377

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
PhyloP100		-0.84
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: rs7003908; hg19: chr8-48770702;