Variant X-73842484-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NR_001564.2(XIST):n.10270C>T 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 0.019 in 551,834 control chromosomes in the GnomAD database, including 111 homozygotes. There are 3,575 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.016 ( 20 hom., 552 hem., cov: 23)

Exomes 𝑓: 0.020 ( 91 hom. 3023 hem. )

Consequence

XIST
NR_001564.2 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.118

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=-0.88).

BP6

Variant X-73842484-G-A is Benign according to our data. Variant chrX-73842484-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041442.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0164 (1832/111438) while in subpopulation NFE AF= 0.0244 (1296/53114). AF 95% confidence interval is 0.0233. There are 20 homozygotes in gnomad4. There are 552 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIST	NR_001564.2 linkuse as main transcript	n.10270C>T		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.10240C>T		non_coding_transcript_exon_variant	1/6	1

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

1831

AN:

111391

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

551

AN XY:

33595

show subpopulations

Gnomad AFR

AF:

0.00320

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00835

Gnomad ASJ

AF:

0.0125

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00301

Gnomad FIN

AF:

0.0482

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0244

Gnomad OTH

AF:

0.0146

GnomAD3 exomes

AF:

0.0158

AC:

2427

AN:

153598

Hom.:

AF XY:

0.0149

AC XY:

775

AN XY:

51860

show subpopulations

Gnomad AFR exome

AF:

0.00320

Gnomad AMR exome

AF:

0.00554

Gnomad ASJ exome

AF:

0.00881

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00553

Gnomad FIN exome

AF:

0.0540

Gnomad NFE exome

AF:

0.0233

Gnomad OTH exome

AF:

0.0156

GnomAD4 exome

AF:

0.0196

AC:

8640

AN:

440396

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

3023

AN XY:

163290

show subpopulations

Gnomad4 AFR exome

AF:

0.00345

Gnomad4 AMR exome

AF:

0.00582

Gnomad4 ASJ exome

AF:

0.00947

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00585

Gnomad4 FIN exome

AF:

0.0538

Gnomad4 NFE exome

AF:

0.0239

Gnomad4 OTH exome

AF:

0.0174

GnomAD4 genome

AF:

0.0164

AC:

1832

AN:

111438

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

552

AN XY:

33652

show subpopulations

Gnomad4 AFR

AF:

0.00319

Gnomad4 AMR

AF:

0.00834

Gnomad4 ASJ

AF:

0.0125

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00340

Gnomad4 FIN

AF:

0.0482

Gnomad4 NFE

AF:

0.0244

Gnomad4 OTH

AF:

0.0144

Alfa

AF:

0.0192

Hom.:

155

Bravo

AF:

0.0136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

XIST-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 14, 2019

This variant is classified as likely 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

-0.88

CADD

Benign

1.3

DANN

Benign

0.39

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