rs2355676

Variant names:

• chrX-123885267-A-G
• rs2355676
• NM_001167.4:c.-32-364A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-123885267-A-G
• chrX-123885267-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167.4(XIAP):​c.-32-364A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 110,876 control chromosomes in the GnomAD database, including 6,087 homozygotes. There are 12,138 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 (6087 hom., 12138 hem., cov: 23)
• Consequence: XIAP NM_001167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495
• Publications: 2 publications found

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]

XIAP Gene-Disease associations (from GenCC):

• X-linked lymphoproliferative disease due to XIAP deficiency

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167.4. 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
	XIAP	NM_001167.4	MANE Select	c.-32-364A>G		intron	N/A	NP_001158.2
	XIAP	NM_001204401.2		c.-32-364A>G		intron	N/A	NP_001191330.1
	XIAP	NM_001378590.1		c.-32-364A>G		intron	N/A	NP_001365519.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIAP	ENST00000371199.8	TSL:1 MANE Select	c.-32-364A>G		intron	N/A	ENSP00000360242.3
	XIAP	ENST00000497640.1	TSL:1	n.100-3352A>G		intron	N/A
	XIAP	ENST00000355640.3	TSL:5	c.-32-364A>G		intron	N/A	ENSP00000347858.3

Frequencies

GnomAD3 genomes AF: 0.381 AC: 42231 AN: 110823 Hom.: 6080 Cov.: 23

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.381 AC: 42254 AN: 110876 Hom.: 6087 Cov.: 23 AF XY: 0.366 AC XY: 12138 AN XY: 33158

African (AFR) AF: 0.473 AC: 14462 AN: 30564

American (AMR) AF: 0.353 AC: 3639 AN: 10309

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 904 AN: 2635

East Asian (EAS) AF: 0.0854 AC: 305 AN: 3572

South Asian (SAS) AF: 0.166 AC: 456 AN: 2742

European-Finnish (FIN) AF: 0.392 AC: 2275 AN: 5798

Middle Eastern (MID) AF: 0.280 AC: 60 AN: 214

European-Non Finnish (NFE) AF: 0.367 AC: 19420 AN: 52861

Other (OTH) AF: 0.372 AC: 560 AN: 1507

Alfa AF: 0.375 Hom.: 3276

Bravo AF: 0.388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.7
DANN	Benign	0.90
PhyloP100		0.49
Mutation Taster		=100/0	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: rs2355676; hg19: chrX-123019117;