rs1794213

Positions:

• chrX-73825905-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000429829.6(XIST):​n.13996T>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 0.0978 in 557,191 control chromosomes in the GnomAD database, including 2,015 homozygotes. There are 19,008 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (549 hom., 3473 hem., cov: 23)
  • Exomes 𝑓: 0.095 (1466 hom. 15535 hem.)
• Consequence: XIST ENST00000429829.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.32

Genes affected

XIST (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIST	NR_001564.2	n.14026T>G		non_coding_transcript_exon_variant	6/6
TSIX	NR_003255.2	n.33701A>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIST	ENST00000429829.6	n.13996T>G		non_coding_transcript_exon_variant	6/6	1
TSIX	ENST00000604411.1	n.33701A>C		non_coding_transcript_exon_variant	1/1	6
XIST	ENST00000648970.1	n.3960T>G		non_coding_transcript_exon_variant	7/7

Frequencies

GnomAD3 genomes AF: 0.109 AC: 12234 AN: 111857 Hom.: 549 Cov.: 23 AF XY: 0.102 AC XY: 3465 AN XY: 34023

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0498

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.00813

Gnomad SAS AF: 0.0687

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.0542

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0852

GnomAD3 exomes AF: 0.0911 AC: 15036 AN: 165012 Hom.: 524 AF XY: 0.0879 AC XY: 5507 AN XY: 62622

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.0784

Gnomad ASJ exome AF: 0.0607

Gnomad EAS exome AF: 0.00622

Gnomad SAS exome AF: 0.0731

Gnomad FIN exome AF: 0.0988

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.0828

GnomAD4 exome AF: 0.0948 AC: 42228 AN: 445278 Hom.: 1466 Cov.: 0 AF XY: 0.0928 AC XY: 15535 AN XY: 167350

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.0818

Gnomad4 ASJ exome AF: 0.0618

Gnomad4 EAS exome AF: 0.00291

Gnomad4 SAS exome AF: 0.0743

Gnomad4 FIN exome AF: 0.0990

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.0947

GnomAD4 genome AF: 0.109 AC: 12249 AN: 111913 Hom.: 549 Cov.: 23 AF XY: 0.102 AC XY: 3473 AN XY: 34089

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0984

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.00815

Gnomad4 SAS AF: 0.0693

Gnomad4 FIN AF: 0.0902

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.106 Hom.: 1977

Bravo AF: 0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1794213; hg19: chrX-73045740;