rs28382739

Positions:

• chrX-123906879-C-T

Variant summary

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

The NM_001167.4(XIAP):​c.1301-109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 920,074 control chromosomes in the GnomAD database, including 15,065 homozygotes. There are 58,099 hemizygotes in GnomAD. 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 0.20 (1514 hom., 6907 hem., cov: 23)
  • Exomes 𝑓: 0.21 (13551 hom. 51192 hem.)
• Consequence: XIAP NM_001167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

XIAP (HGNC:592): (X-linked inhibitor of apoptosis) This gene encodes a protein that belongs to a family of apoptotic suppressor proteins. Members of this family share a conserved motif termed, baculovirus IAP repeat, which is necessary for their anti-apoptotic function. This protein functions through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2 and inhibits apoptosis induced by menadione, a potent inducer of free radicals, and interleukin 1-beta converting enzyme. This protein also inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. Mutations in this gene are the cause of X-linked lymphoproliferative syndrome. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 2 and 11.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XIAP	NM_001167.4	c.1301-109C>T		intron_variant		ENST00000371199.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XIAP	ENST00000371199.8	c.1301-109C>T		intron_variant		1	NM_001167.4	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 21940 AN: 111655 Hom.: 1514 Cov.: 23 AF XY: 0.204 AC XY: 6895 AN XY: 33871

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.214 AC: 172663 AN: 808365 Hom.: 13551 AF XY: 0.230 AC XY: 51192 AN XY: 222279

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.196 AC: 21947 AN: 111709 Hom.: 1514 Cov.: 23 AF XY: 0.204 AC XY: 6907 AN XY: 33935

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.210

Alfa AF: 0.191 Hom.: 1131

Bravo AF: 0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.72

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: rs28382739; hg19: chrX-123040729; COSMIC: COSV63022430;