rs2905404

chrX-113898791-G-AchrX-113898791-G-C

Variant summary

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

The ENST00000468762.3(XACT):n.293+39402C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 109,829 control chromosomes in the GnomAD database, including 11,703 homozygotes. There are 16,681 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 0.51 (11703 hom., 16681 hem., cov: 22)
• Consequence: XACT ENST00000468762.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

Genes affected

XACT (HGNC:45056): (X active specific transcript) This gene produces a spliced long non-coding RNA that is thought to play a role in the control of X-chromosome inactivation (XCI). This transcript has been shown to specifically coat the active X chromosome in human pluripotent cells. [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XACT	ENST00000468762.3	n.293+39402C>T		intron_variant, non_coding_transcript_variant		5
XACT	ENST00000674361.1	n.65070C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.509 AC: 55864 AN: 109781 Hom.: 11707 Cov.: 22 AF XY: 0.520 AC XY: 16667 AN XY: 32055

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.530

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.509 AC: 55866 AN: 109829 Hom.: 11703 Cov.: 22 AF XY: 0.519 AC XY: 16681 AN XY: 32113

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.535

Alfa AF: 0.605 Hom.: 30332

Bravo AF: 0.486

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2905404; hg19: chrX-113142068;