chr5-10761070-A-G

Variant names:

• chr5-10761070-A-G
• rs267927
• NM_004394.3:c.-2T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004394.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAP	NM_004394.3	MANE Select	c.-2T>C		5_prime_UTR	Exon 1 of 4	NP_004385.1
	DAP-DT	NR_187555.1		n.35A>G		non_coding_transcript_exon	Exon 1 of 3
	DAP	NM_001291963.2		c.-2T>C		5_prime_UTR	Exon 1 of 3	NP_001278892.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAP	ENST00000230895.11	TSL:1 MANE Select	c.-2T>C		5_prime_UTR	Exon 1 of 4	ENSP00000230895.7
	DAP	ENST00000508253.5	TSL:2	n.156T>C		non_coding_transcript_exon	Exon 1 of 3
	DAP	ENST00000508646.1	TSL:2	n.32T>C		non_coding_transcript_exon	Exon 1 of 2

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

GnomAD2 exomes AF: 0.946 AC: 56027 AN: 59220 AF XY: 0.947

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 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

African (AFR) AF: 0.978 AC: 21534 AN: 22024

American (AMR) AF: 0.925 AC: 8705 AN: 9414

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 11662 AN: 11682

East Asian (EAS) AF: 0.646 AC: 15528 AN: 24026

South Asian (SAS) AF: 0.851 AC: 18897 AN: 22208

European-Finnish (FIN) AF: 0.983 AC: 34179 AN: 34780

Middle Eastern (MID) AF: 0.983 AC: 2629 AN: 2674

European-Non Finnish (NFE) AF: 0.996 AC: 897321 AN: 901010

Other (OTH) AF: 0.964 AC: 38809 AN: 40274

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

African (AFR) AF: 0.979 AC: 40424 AN: 41290

American (AMR) AF: 0.958 AC: 14494 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3422 AN: 3428

East Asian (EAS) AF: 0.660 AC: 3343 AN: 5066

South Asian (SAS) AF: 0.843 AC: 4063 AN: 4818

European-Finnish (FIN) AF: 0.980 AC: 9667 AN: 9866

Middle Eastern (MID) AF: 0.990 AC: 289 AN: 292

European-Non Finnish (NFE) AF: 0.996 AC: 66909 AN: 67210

Other (OTH) AF: 0.968 AC: 2018 AN: 2084

Alfa AF: 0.987 Hom.: 10351

Asia WGS AF: 0.790 AC: 2462 AN: 3114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		0.12
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	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: rs267927; hg19: chr5-10761182; COSMIC: COSV50143132;