rs267927

chr5-10761070-A-G

Variant summary

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

The NM_004394.3(DAP):c.-2T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.981 in 1,218,190 control chromosomes in the GnomAD database, including 588,041 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 0.97 (70881 hom., cov: 31)
  • Exomes 𝑓: 0.98 (517160 hom.)
• Consequence: DAP NM_004394.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

Genes affected

DAP (HGNC:2672): (death associated protein) This gene encodes a basic, proline-rich, 15-kD protein. The protein acts as a positive mediator of programmed cell death that is induced by interferon-gamma. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

DAP-DT (HGNC:55214): (DAP divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAP	NM_004394.3	c.-2T>C		5_prime_UTR_variant	1/4	ENST00000230895.11
DAP-DT	XR_007058693.1	n.96+3130A>G		intron_variant, non_coding_transcript_variant
DAP	NM_001291963.2	c.-2T>C		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAP	ENST00000230895.11	c.-2T>C		5_prime_UTR_variant	1/4	1	NM_004394.3	P1
DAP-DT	ENST00000606513.5	n.6A>G		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes AF: 0.970 AC: 145432 AN: 149992 Hom.: 70827 Cov.: 31

Gnomad AFR AF: 0.979

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.968

GnomAD3 exomes AF: 0.946 AC: 56027 AN: 59220 Hom.: 26828 AF XY: 0.947 AC XY: 29955 AN XY: 31618

Gnomad AFR exome AF: 0.973

Gnomad AMR exome AF: 0.905

Gnomad ASJ exome AF: 0.997

Gnomad EAS exome AF: 0.614

Gnomad SAS exome AF: 0.811

Gnomad FIN exome AF: 0.981

Gnomad NFE exome AF: 0.994

Gnomad OTH exome AF: 0.959

GnomAD4 exome AF: 0.982 AC: 1049264 AN: 1068092 Hom.: 517160 Cov.: 30 AF XY: 0.982 AC XY: 499365 AN XY: 508548

Gnomad4 AFR exome AF: 0.978

Gnomad4 AMR exome AF: 0.925

Gnomad4 ASJ exome AF: 0.998

Gnomad4 EAS exome AF: 0.646

Gnomad4 SAS exome AF: 0.851

Gnomad4 FIN exome AF: 0.983

Gnomad4 NFE exome AF: 0.996

Gnomad4 OTH exome AF: 0.964

GnomAD4 genome AF: 0.970 AC: 145539 AN: 150098 Hom.: 70881 Cov.: 31 AF XY: 0.965 AC XY: 70652 AN XY: 73236

Gnomad4 AFR AF: 0.979

Gnomad4 AMR AF: 0.958

Gnomad4 ASJ AF: 0.998

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.980

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.968

Alfa AF: 0.987 Hom.: 10351

Asia WGS AF: 0.790 AC: 2462 AN: 3114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	13
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs267927; hg19: chr5-10761182; COSMIC: COSV50143132;