Variant rs28382742 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.*803G>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 0.17 ( 1440 hom., 3849 hem., cov: 20)

Exomes 𝑓: 0.21 ( 3898 hom. 21810 hem. )

Consequence

XIAP
NM_001167.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.392

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=-0.91).

BP6

Variant X-123907984-G-T is Benign according to our data. Variant chrX-123907984-G-T is described in ClinVar as [Benign]. Clinvar id is 367801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 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.*803G>T		3_prime_UTR_variant	7/7	ENST00000371199.8	NP_001158.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
XIAP	ENST00000371199.8 linkuse as main transcript	c.*803G>T	3_prime_UTR_variant	7/7	1	NM_001167.4	ENSP00000360242	P1
XIAP	ENST00000355640.3 linkuse as main transcript	c.*803G>T	3_prime_UTR_variant	7/7	5		ENSP00000347858	P1
XIAP	ENST00000422098.6 linkuse as main transcript	c.*803G>T	3_prime_UTR_variant	9/9	4		ENSP00000405529	P1

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

18263

AN:

106197

Hom.:

1442

Cov.:

AF XY:

0.131

AC XY:

3843

AN XY:

29365

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.279

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.237

AC:

20842

AN:

88057

Hom.:

1809

AF XY:

0.242

AC XY:

7495

AN XY:

30911

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.367

Gnomad SAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.246

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.211

AC:

52911

AN:

250214

Hom.:

3898

Cov.:

AF XY:

0.234

AC XY:

21810

AN XY:

93330

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.268

Gnomad4 SAS exome

AF:

0.384

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.174

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.172

AC:

18259

AN:

106228

Hom.:

1440

Cov.:

AF XY:

0.131

AC XY:

3849

AN XY:

29412

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.296

Gnomad4 SAS

AF:

0.316

Gnomad4 FIN

AF:

0.174

Gnomad4 NFE

AF:

0.180

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.194

Hom.:

1689

Bravo

AF:

0.191

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

-0.91

CADD

Benign

0.42

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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