9-87578076-C-T

Position:

• chr9-87578076-C-T

Variant summary

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

The NM_004938.4(DAPK1):​c.63-26878C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,860 control chromosomes in the GnomAD database, including 13,094 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 0.41 (13094 hom., cov: 31)
• Consequence: DAPK1 NM_004938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

Genes affected

DAPK1 (HGNC:2674): (death associated protein kinase 1) Death-associated protein kinase 1 is a positive mediator of gamma-interferon induced programmed cell death. DAPK1 encodes a structurally unique 160-kD calmodulin dependent serine-threonine kinase that carries 8 ankyrin repeats and 2 putative P-loop consensus sites. It is a tumor suppressor candidate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPK1	NM_004938.4	c.63-26878C>T		intron_variant		ENST00000408954.8	NP_004929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAPK1	ENST00000408954.8	c.63-26878C>T		intron_variant		2	NM_004938.4	ENSP00000386135	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61596 AN: 151742 Hom.: 13081 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.406 AC: 61643 AN: 151860 Hom.: 13094 Cov.: 31 AF XY: 0.414 AC XY: 30709 AN XY: 74228

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.448

Alfa AF: 0.377 Hom.: 14199

Bravo AF: 0.410

Asia WGS AF: 0.617 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.81

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: rs4878104; hg19: chr9-90192991;