Variant X-123911791-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.671

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIAP	NM_001167.4 link	c.*4610C>T		3_prime_UTR_variant	7/7	ENST00000371199.8	NP_001158.2	P98170

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIAP	ENST00000371199.8 link	c.*4610C>T		3_prime_UTR_variant	7/7	1	NM_001167.4	ENSP00000360242.3		P98170
XIAP	ENST00000355640.3 link	c.*4610C>T		3_prime_UTR_variant	7/7	5		ENSP00000347858.3		P98170

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

65961

AN:

110731

Hom.:

13951

Cov.:

AF XY:

0.596

AC XY:

19661

AN XY:

32983

show subpopulations

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

GnomAD3 exomes

AF:

0.566

AC:

52567

AN:

92905

Hom.:

9385

AF XY:

0.566

AC XY:

19819

AN XY:

35001

show subpopulations

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 SAS exome

AF:

0.593

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.:

AF XY:

0.572

AC XY:

49131

AN XY:

85940

show subpopulations

Gnomad4 AFR exome

AF:

0.677

Gnomad4 AMR exome

AF:

0.549

Gnomad4 ASJ exome

AF:

0.545

Gnomad4 EAS exome

AF:

0.455

Gnomad4 SAS exome

AF:

0.593

Gnomad4 FIN exome

AF:

0.653

Gnomad4 NFE exome

AF:

0.564

Gnomad4 OTH exome

AF:

0.575

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.596

AC:

66006

AN:

110785

Hom.:

13951

Cov.:

AF XY:

0.596

AC XY:

19708

AN XY:

33047

show subpopulations

Gnomad4 AFR

AF:

0.674

Gnomad4 AMR

AF:

0.588

Gnomad4 ASJ

AF:

0.534

Gnomad4 EAS

AF:

0.427

Gnomad4 SAS

AF:

0.563

Gnomad4 FIN

AF:

0.663

Gnomad4 NFE

AF:

0.563

Gnomad4 OTH

AF:

0.591

Alfa

AF:

0.565

Hom.:

49493

Bravo

AF:

0.596

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

X-linked lymphoproliferative disease due to XIAP deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.0

DANN

Benign

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over