rs28382701

Variant names:

• chrX-123859895-C-G
• rs28382701
• NM_001204401.2:c.-43C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-123859895-C-G
• chrX-123859895-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001204401.2(XIAP):​c.-43C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 24)
• Consequence: XIAP NM_001204401.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XIAP	NM_001204401.2	c.-43C>G		5_prime_UTR_variant	Exon 1 of 7		NP_001191330.1
XIAP	NM_001378591.1	c.-170C>G		5_prime_UTR_variant	Exon 1 of 8		NP_001365520.1
XIAP	NM_001378592.1	c.-33+157C>G		intron_variant	Intron 1 of 6		NP_001365521.1
XIAP	NR_165803.1	n.86C>G		non_coding_transcript_exon_variant	Exon 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XIAP	ENST00000422098	c.-170C>G		5_prime_UTR_variant	Exon 2 of 9	4		ENSP00000405529.2
XIAP	ENST00000430625	c.-43C>G		5_prime_UTR_variant	Exon 1 of 2	3		ENSP00000400637.1
XIAP	ENST00000468691.5	n.19C>G		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.12
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: rs28382701; hg19: chrX-122993745;