rs8371

Variant names:

• chrX-123912065-C-T
• rs8371
• NM_001167.4:c.*4884C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-123912065-C-T
• chrX-123912065-C-A

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.*4884C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 325,624 control chromosomes in the GnomAD database, including 5,174 homozygotes. There are 28,453 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (1512 hom., 6360 hem., cov: 21)
  • Exomes 𝑓: 0.24 (3662 hom. 22093 hem.)
• Consequence: XIAP NM_001167.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.793
• Publications: 8 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=-0.88).
• BP6: Variant X-123912065-C-T is Benign according to our data. Variant chrX-123912065-C-T is described in ClinVar as Benign. ClinVar VariationId is 367838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.365 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.*4884C>T		3_prime_UTR	Exon 7 of 7	NP_001158.2
	XIAP	NM_001204401.2		c.*4884C>T		3_prime_UTR	Exon 7 of 7	NP_001191330.1	P98170
	XIAP	NM_001378590.1		c.*4884C>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.*4884C>T		3_prime_UTR	Exon 7 of 7	ENSP00000360242.3	P98170
	XIAP	ENST00000355640.3	TSL:5	c.*4884C>T		3_prime_UTR	Exon 7 of 7	ENSP00000347858.3	P98170

Frequencies

GnomAD3 genomes AF: 0.195 AC: 21409 AN: 109835 Hom.: 1512 Cov.: 21

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.203

GnomAD2 exomes AF: 0.245 AC: 23237 AN: 94756 AF XY: 0.258

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.374

Gnomad FIN exome AF: 0.250

Gnomad NFE exome AF: 0.197

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.237 AC: 51119 AN: 215751 Hom.: 3662 Cov.: 0 AF XY: 0.257 AC XY: 22093 AN XY: 85953

African (AFR) AF: 0.154 AC: 1052 AN: 6832

American (AMR) AF: 0.211 AC: 4532 AN: 21437

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 1623 AN: 7975

East Asian (EAS) AF: 0.363 AC: 2428 AN: 6684

South Asian (SAS) AF: 0.387 AC: 13792 AN: 35631

European-Finnish (FIN) AF: 0.245 AC: 2305 AN: 9399

Middle Eastern (MID) AF: 0.287 AC: 236 AN: 823

European-Non Finnish (NFE) AF: 0.196 AC: 22789 AN: 116541

Other (OTH) AF: 0.226 AC: 2362 AN: 10429

GnomAD4 genome AF: 0.195 AC: 21409 AN: 109873 Hom.: 1512 Cov.: 21 AF XY: 0.198 AC XY: 6360 AN XY: 32157

African (AFR) AF: 0.148 AC: 4475 AN: 30258

American (AMR) AF: 0.222 AC: 2260 AN: 10196

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 502 AN: 2634

East Asian (EAS) AF: 0.335 AC: 1164 AN: 3472

South Asian (SAS) AF: 0.385 AC: 988 AN: 2568

European-Finnish (FIN) AF: 0.251 AC: 1408 AN: 5600

Middle Eastern (MID) AF: 0.314 AC: 65 AN: 207

European-Non Finnish (NFE) AF: 0.192 AC: 10117 AN: 52758

Other (OTH) AF: 0.210 AC: 315 AN: 1503

Alfa AF: 0.191 Hom.: 4271

Bravo AF: 0.193

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	-0.88
CADD	Benign	6.1
DANN	Benign	0.71
PhyloP100		0.79
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: rs8371; hg19: chrX-123045915;