rs28382742

Variant names:

• chrX-123907984-G-T
• rs28382742
• NM_001167.4:c.*803G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001167.4(XIAP):​c.*803G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (1440 hom., 3849 hem., cov: 20)
  • Exomes 𝑓: 0.21 (3898 hom. 21810 hem.)
• Consequence: XIAP NM_001167.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.392
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-123907984-G-T is Benign according to our data. Variant chrX-123907984-G-T is described in ClinVar as Benign. ClinVar VariationId is 367801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIAP	NM_001167.4	MANE Select	c.*803G>T		3_prime_UTR	Exon 7 of 7	NP_001158.2
	XIAP	NM_001204401.2		c.*803G>T		3_prime_UTR	Exon 7 of 7	NP_001191330.1	P98170
	XIAP	NM_001378590.1		c.*803G>T		3_prime_UTR	Exon 7 of 7	NP_001365519.1	P98170

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIAP	ENST00000371199.8	TSL:1 MANE Select	c.*803G>T		3_prime_UTR	Exon 7 of 7	ENSP00000360242.3	P98170
	XIAP	ENST00000355640.3	TSL:5	c.*803G>T		3_prime_UTR	Exon 7 of 7	ENSP00000347858.3	P98170
	XIAP	ENST00000422098.6	TSL:4	c.*803G>T		3_prime_UTR	Exon 9 of 9	ENSP00000405529.2	P98170

Frequencies

GnomAD3 genomes AF: 0.172 AC: 18263 AN: 106197 Hom.: 1442 Cov.: 20

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.180

GnomAD2 exomes AF: 0.237 AC: 20842 AN: 88057 AF XY: 0.242

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.367

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.225

GnomAD4 exome AF: 0.211 AC: 52911 AN: 250214 Hom.: 3898 Cov.: 0 AF XY: 0.234 AC XY: 21810 AN XY: 93330

African (AFR) AF: 0.121 AC: 1022 AN: 8476

American (AMR) AF: 0.198 AC: 4289 AN: 21696

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 1702 AN: 9996

East Asian (EAS) AF: 0.268 AC: 3326 AN: 12410

South Asian (SAS) AF: 0.384 AC: 13363 AN: 34796

European-Finnish (FIN) AF: 0.244 AC: 2277 AN: 9330

Middle Eastern (MID) AF: 0.248 AC: 245 AN: 986

European-Non Finnish (NFE) AF: 0.174 AC: 24139 AN: 139012

Other (OTH) AF: 0.189 AC: 2548 AN: 13512

GnomAD4 genome AF: 0.172 AC: 18259 AN: 106228 Hom.: 1440 Cov.: 20 AF XY: 0.131 AC XY: 3849 AN XY: 29412

African (AFR) AF: 0.126 AC: 3712 AN: 29453

American (AMR) AF: 0.185 AC: 1781 AN: 9640

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 468 AN: 2582

East Asian (EAS) AF: 0.296 AC: 963 AN: 3248

South Asian (SAS) AF: 0.316 AC: 710 AN: 2245

European-Finnish (FIN) AF: 0.174 AC: 888 AN: 5090

Middle Eastern (MID) AF: 0.278 AC: 57 AN: 205

European-Non Finnish (NFE) AF: 0.180 AC: 9313 AN: 51665

Other (OTH) AF: 0.186 AC: 268 AN: 1442

Alfa AF: 0.194 Hom.: 1689

Bravo AF: 0.191

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	X-linked lymphoproliferative disease due to XIAP deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.52
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs28382742; hg19: chrX-123041834;