rs9856

Variant names:

• chrX-123911791-C-T
• rs9856
• NM_001167.4:c.*4610C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-123911791-C-T
• chrX-123911791-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.*4610C>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 0.60 (13951 hom., 19708 hem., cov: 23)
  • Exomes 𝑓: 0.57 (21409 hom. 49131 hem.)
  • Failed GnomAD Quality Control
• Consequence: XIAP NM_001167.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.671
• Publications: 7 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=-0.92).
• BP6: Variant X-123911791-C-T is Benign according to our data. Variant chrX-123911791-C-T is described in ClinVar as Benign. ClinVar VariationId is 367837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 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.*4610C>T		3_prime_UTR	Exon 7 of 7	NP_001158.2
	XIAP	NM_001204401.2		c.*4610C>T		3_prime_UTR	Exon 7 of 7	NP_001191330.1	P98170
	XIAP	NM_001378590.1		c.*4610C>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.*4610C>T		3_prime_UTR	Exon 7 of 7	ENSP00000360242.3	P98170
	XIAP	ENST00000355640.3	TSL:5	c.*4610C>T		3_prime_UTR	Exon 7 of 7	ENSP00000347858.3	P98170

Frequencies

GnomAD3 genomes AF: 0.596 AC: 65961 AN: 110731 Hom.: 13951 Cov.: 23

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.590

GnomAD2 exomes AF: 0.566 AC: 52567 AN: 92905 AF XY: 0.566

Gnomad AFR exome AF: 0.672

Gnomad AMR exome AF: 0.552

Gnomad ASJ exome AF: 0.546

Gnomad EAS exome AF: 0.468

Gnomad FIN exome AF: 0.648

Gnomad NFE exome AF: 0.564

Gnomad OTH exome AF: 0.563

GnomAD4 exome AF: 0.571 AC: 123225 AN: 215734 Hom.: 21409 Cov.: 0 AF XY: 0.572 AC XY: 49131 AN XY: 85940

African (AFR) AF: 0.677 AC: 4624 AN: 6834

American (AMR) AF: 0.549 AC: 11776 AN: 21441

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 4348 AN: 7974

East Asian (EAS) AF: 0.455 AC: 3038 AN: 6684

South Asian (SAS) AF: 0.593 AC: 21139 AN: 35622

European-Finnish (FIN) AF: 0.653 AC: 6139 AN: 9398

Middle Eastern (MID) AF: 0.569 AC: 468 AN: 822

European-Non Finnish (NFE) AF: 0.564 AC: 65690 AN: 116528

Other (OTH) AF: 0.575 AC: 6003 AN: 10431

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.596 AC: 66006 AN: 110785 Hom.: 13951 Cov.: 23 AF XY: 0.596 AC XY: 19708 AN XY: 33047

African (AFR) AF: 0.674 AC: 20561 AN: 30526

American (AMR) AF: 0.588 AC: 6091 AN: 10366

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1407 AN: 2636

East Asian (EAS) AF: 0.427 AC: 1505 AN: 3521

South Asian (SAS) AF: 0.563 AC: 1499 AN: 2663

European-Finnish (FIN) AF: 0.663 AC: 3870 AN: 5838

Middle Eastern (MID) AF: 0.624 AC: 133 AN: 213

European-Non Finnish (NFE) AF: 0.563 AC: 29747 AN: 52828

Other (OTH) AF: 0.591 AC: 902 AN: 1526

Alfa AF: 0.574 Hom.: 67854

Bravo AF: 0.596

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	-0.92
CADD	Benign	4.0
DANN	Benign	0.57
PhyloP100		0.67
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: rs9856; hg19: chrX-123045641;