Variant rs12838858 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001167.4(XIAP):c.*80G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 915,101 control chromosomes in the GnomAD database, including 2,669 homozygotes. There are 21,564 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.060 ( 213 hom., 1974 hem., cov: 23)

Exomes 𝑓: 0.088 ( 2456 hom. 19590 hem. )

Consequence

XIAP
NM_001167.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0530

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-123907261-G-C is Benign according to our data. Variant chrX-123907261-G-C is described in ClinVar as [Benign]. Clinvar id is 367797.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XIAP	NM_001167.4 linkuse as main transcript	c.*80G>C		3_prime_UTR_variant	7/7	ENST00000371199.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XIAP	ENST00000371199.8 linkuse as main transcript	c.*80G>C		3_prime_UTR_variant	7/7	1	NM_001167.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0605

AC:

6748

AN:

111529

Hom.:

213

Cov.:

AF XY:

0.0585

AC XY:

1974

AN XY:

33745

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.00878

Gnomad AMR

AF:

0.0458

Gnomad ASJ

AF:

0.0557

Gnomad EAS

AF:

0.000559

Gnomad SAS

AF:

0.0335

Gnomad FIN

AF:

0.0981

Gnomad MID

AF:

0.0336

Gnomad NFE

AF:

0.0930

Gnomad OTH

AF:

0.0514

GnomAD3 exomes

AF:

0.0637

AC:

8444

AN:

132506

Hom.:

232

AF XY:

0.0645

AC XY:

2656

AN XY:

41164

show subpopulations

Gnomad AFR exome

AF:

0.0121

Gnomad AMR exome

AF:

0.0295

Gnomad ASJ exome

AF:

0.0504

Gnomad EAS exome

AF:

0.000199

Gnomad SAS exome

AF:

0.0481

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.0941

Gnomad OTH exome

AF:

0.0597

GnomAD4 exome

AF:

0.0883

AC:

70937

AN:

803518

Hom.:

2456

Cov.:

AF XY:

0.0922

AC XY:

19590

AN XY:

212424

show subpopulations

Gnomad4 AFR exome

AF:

0.0139

Gnomad4 AMR exome

AF:

0.0299

Gnomad4 ASJ exome

AF:

0.0515

Gnomad4 EAS exome

AF:

0.000584

Gnomad4 SAS exome

AF:

0.0499

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.0772

GnomAD4 genome

AF:

0.0605

AC:

6749

AN:

111583

Hom.:

213

Cov.:

AF XY:

0.0584

AC XY:

1974

AN XY:

33809

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.0457

Gnomad4 ASJ

AF:

0.0557

Gnomad4 EAS

AF:

0.000560

Gnomad4 SAS

AF:

0.0333

Gnomad4 FIN

AF:

0.0981

Gnomad4 NFE

AF:

0.0930

Gnomad4 OTH

AF:

0.0514

Alfa

AF:

0.0417

Hom.:

301

Bravo

AF:

0.0551

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.82

CADD

Benign

7.7

DANN

Benign

0.79

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