Variant X-123912065-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.*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

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.793

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:

XIAP (HGNC:):

XIAP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIAP	NM_001167.4 linkuse as main transcript	c.*4884C>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 linkuse as main transcript	c.*4884C>T		3_prime_UTR_variant	7/7	1	NM_001167.4	ENSP00000360242.3		P98170
XIAP	ENST00000355640.3 linkuse as main transcript	c.*4884C>T		3_prime_UTR_variant	7/7	5		ENSP00000347858.3		P98170

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

21409

AN:

109835

Hom.:

1512

Cov.:

AF XY:

0.198

AC XY:

6355

AN XY:

32109

show subpopulations

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

GnomAD3 exomes

AF:

0.245

AC:

23237

AN:

94756

Hom.:

1877

AF XY:

0.258

AC XY:

9165

AN XY:

35542

show subpopulations

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 SAS exome

AF:

0.396

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.:

AF XY:

0.257

AC XY:

22093

AN XY:

85953

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.363

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.245

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.226

GnomAD4 genome

AF:

0.195

AC:

21409

AN:

109873

Hom.:

1512

Cov.:

AF XY:

0.198

AC XY:

6360

AN XY:

32157

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.222

Gnomad4 ASJ

AF:

0.191

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.385

Gnomad4 FIN

AF:

0.251

Gnomad4 NFE

AF:

0.192

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.191

Hom.:

3931

Bravo

AF:

0.193

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

-0.88

CADD

Benign

6.1

DANN

Benign

0.71

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