rs1474593

Positions:

• chrX-123861754-T-C

Variant summary

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

The NM_001167.4(XIAP):​c.-33+1461T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 110,953 control chromosomes in the GnomAD database, including 6,126 homozygotes. There are 12,242 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 0.38 (6126 hom., 12242 hem., cov: 23)
• Consequence: XIAP NM_001167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XIAP	NM_001167.4	c.-33+1461T>C		intron_variant		ENST00000371199.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XIAP	ENST00000371199.8	c.-33+1461T>C		intron_variant		1	NM_001167.4	P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 42421 AN: 110901 Hom.: 6120 Cov.: 23 AF XY: 0.369 AC XY: 12223 AN XY: 33159

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.0843

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.383 AC: 42443 AN: 110953 Hom.: 6126 Cov.: 23 AF XY: 0.369 AC XY: 12242 AN XY: 33221

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.0840

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.373

Alfa AF: 0.387 Hom.: 2582

Bravo AF: 0.389

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.71

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: rs1474593; hg19: chrX-122995604;