Variant X-73820953-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000429829.6(XIST):n.18948T>C 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 0.00395 in 557,636 control chromosomes in the GnomAD database, including 29 homozygotes. There are 560 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 0.012 ( 22 hom., 352 hem., cov: 23)

Exomes 𝑓: 0.0018 ( 7 hom. 208 hem. )

Consequence

XIST
ENST00000429829.6 non_coding_transcript_exon

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

XIST (HGNC:):

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=-0.58).

BP6

Variant X-73820953-A-G is Benign according to our data. Variant chrX-73820953-A-G is described in ClinVar as [Benign]. Clinvar id is 3042649.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1398/112518) while in subpopulation AFR AF= 0.0432 (1339/31016). AF 95% confidence interval is 0.0412. There are 22 homozygotes in gnomad4. There are 352 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIST	NR_001564.2 linkuse as main transcript	n.18978T>C		non_coding_transcript_exon_variant	6/6
TSIX	NR_003255.2 linkuse as main transcript	n.28749A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
XIST	ENST00000429829.6 linkuse as main transcript	n.18948T>C	non_coding_transcript_exon_variant	6/6	1
XIST	ENST00000416330.2 linkuse as main transcript	n.608T>C	non_coding_transcript_exon_variant	4/4	2
XIST	ENST00000417942.5 linkuse as main transcript	n.427T>C	non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1401

AN:

112466

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

353

AN XY:

34634

show subpopulations

Gnomad AFR

AF:

0.0434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00387

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000131

Gnomad OTH

AF:

0.00721

GnomAD3 exomes

AF:

0.00331

AC:

547

AN:

165190

Hom.:

AF XY:

0.00237

AC XY:

149

AN XY:

62862

show subpopulations

Gnomad AFR exome

AF:

0.0428

Gnomad AMR exome

AF:

0.00199

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000147

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00181

AC:

805

AN:

445118

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

208

AN XY:

167236

show subpopulations

Gnomad4 AFR exome

AF:

0.0416

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.00399

GnomAD4 genome

AF:

0.0124

AC:

1398

AN:

112518

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

352

AN XY:

34696

show subpopulations

Gnomad4 AFR

AF:

0.0432

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000131

Gnomad4 OTH

AF:

0.00712

Alfa

AF:

0.00513

Hom.:

Bravo

AF:

0.0142

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

Feb 24, 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

-0.58

CADD

Benign

7.8

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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