Variant X-73827734-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000429829.6(XIST):n.12167G>A 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 0.0155 in 546,311 control chromosomes in the GnomAD database, including 387 homozygotes. There are 2,508 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 0.044 ( 266 hom., 1350 hem., cov: 23)

Exomes 𝑓: 0.0083 ( 121 hom. 1158 hem. )

Consequence

XIST
ENST00000429829.6 non_coding_transcript_exon

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.423

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=-0.62).

BP6

Variant X-73827734-C-T is Benign according to our data. Variant chrX-73827734-C-T is described in ClinVar as [Benign]. Clinvar id is 3039573.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 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.12197G>A		non_coding_transcript_exon_variant	6/6
TSIX	NR_003255.2 linkuse as main transcript	n.35530C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
XIST	ENST00000429829.6 linkuse as main transcript	n.12167G>A	non_coding_transcript_exon_variant	6/6	1
XIST	ENST00000421322.3 linkuse as main transcript	n.1339G>A	non_coding_transcript_exon_variant	6/7	2
XIST	ENST00000433732.2 linkuse as main transcript	n.450G>A	non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0441

AC:

4873

AN:

110487

Hom.:

266

Cov.:

AF XY:

0.0411

AC XY:

1352

AN XY:

32857

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.00834

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00814

Gnomad FIN

AF:

0.00120

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.00127

Gnomad OTH

AF:

0.0364

GnomAD3 exomes

AF:

0.0133

AC:

1931

AN:

144850

Hom.:

AF XY:

0.0103

AC XY:

492

AN XY:

47740

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.00931

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00604

Gnomad FIN exome

AF:

0.00122

Gnomad NFE exome

AF:

0.00142

Gnomad OTH exome

AF:

0.00839

GnomAD4 exome

AF:

0.00828

AC:

3607

AN:

435771

Hom.:

121

Cov.:

AF XY:

0.00722

AC XY:

1158

AN XY:

160451

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.00819

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00651

Gnomad4 FIN exome

AF:

0.000787

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.0441

AC:

4871

AN:

110540

Hom.:

266

Cov.:

AF XY:

0.0410

AC XY:

1350

AN XY:

32920

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.0204

Gnomad4 ASJ

AF:

0.00834

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00816

Gnomad4 FIN

AF:

0.00120

Gnomad4 NFE

AF:

0.00127

Gnomad4 OTH

AF:

0.0360

Alfa

AF:

0.0226

Hom.:

167

Bravo

AF:

0.0509

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

Jan 20, 2020

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

-0.62

CADD

Benign

6.3

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.97

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