Variant X-73844076-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NR_001564.2(XIST):n.8678A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 556,619 control chromosomes in the GnomAD database, including 543 homozygotes. There are 10,656 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.039 ( 103 hom., 1213 hem., cov: 23)

Exomes 𝑓: 0.052 ( 440 hom. 9443 hem. )

Consequence

XIST
NR_001564.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.408

Variant links:

Genes affected

XIST (HGNC:12810): (X inactive specific transcript) X inactivation is an early developmental process in mammalian females that transcriptionally silences one of the pair of X chromosomes, thus providing dosage equivalence between males and females. The process is regulated by several factors, including a region of chromosome X called the X inactivation center (XIC). The XIC comprises several non-coding and protein-coding genes, and this gene was the first non-coding gene identified within the XIC. This gene is expressed exclusively from the XIC of the inactive X chromosome, and is essential for the initiation and spread of X-inactivation. The transcript is a spliced RNA. Alternatively spliced transcript variants have been identified, but their full length sequences have not been determined. Mutations in the XIST promoter cause familial skewed X inactivation. [provided by RefSeq, Apr 2012]

XIST links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-73844076-T-C is Benign according to our data. Variant chrX-73844076-T-C is described in ClinVar as [Benign]. Clinvar id is 3056865.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIST	NR_001564.2 linkuse as main transcript	n.8678A>G		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIST	ENST00000429829.6 linkuse as main transcript	n.8648A>G		non_coding_transcript_exon_variant	1/6	1

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

4369

AN:

111185

Hom.:

103

Cov.:

AF XY:

0.0364

AC XY:

1214

AN XY:

33395

show subpopulations

Gnomad AFR

AF:

0.00819

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0384

Gnomad ASJ

AF:

0.0987

Gnomad EAS

AF:

0.000284

Gnomad SAS

AF:

0.0655

Gnomad FIN

AF:

0.0219

Gnomad MID

AF:

0.0901

Gnomad NFE

AF:

0.0557

Gnomad OTH

AF:

0.0596

GnomAD3 exomes

AF:

0.0471

AC:

7889

AN:

167649

Hom.:

125

AF XY:

0.0523

AC XY:

3332

AN XY:

63745

show subpopulations

Gnomad AFR exome

AF:

0.00702

Gnomad AMR exome

AF:

0.0244

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.000378

Gnomad SAS exome

AF:

0.0722

Gnomad FIN exome

AF:

0.0216

Gnomad NFE exome

AF:

0.0588

Gnomad OTH exome

AF:

0.0569

GnomAD4 exome

AF:

0.0522

AC:

23251

AN:

445375

Hom.:

440

Cov.:

AF XY:

0.0564

AC XY:

9443

AN XY:

167445

show subpopulations

Gnomad4 AFR exome

AF:

0.00858

Gnomad4 AMR exome

AF:

0.0267

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.000147

Gnomad4 SAS exome

AF:

0.0769

Gnomad4 FIN exome

AF:

0.0243

Gnomad4 NFE exome

AF:

0.0584

Gnomad4 OTH exome

AF:

0.0556

GnomAD4 genome

AF:

0.0392

AC:

4364

AN:

111244

Hom.:

103

Cov.:

AF XY:

0.0362

AC XY:

1213

AN XY:

33464

show subpopulations

Gnomad4 AFR

AF:

0.00817

Gnomad4 AMR

AF:

0.0383

Gnomad4 ASJ

AF:

0.0987

Gnomad4 EAS

AF:

0.000285

Gnomad4 SAS

AF:

0.0653

Gnomad4 FIN

AF:

0.0219

Gnomad4 NFE

AF:

0.0557

Gnomad4 OTH

AF:

0.0575

Alfa

AF:

0.0561

Hom.:

617

Bravo

AF:

0.0390

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

XIST-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

DANN

Benign

0.51

Splicing

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