chrX-74256575-G-A

Variant names:

• chrX-74256575-G-A
• rs610488
• ENST00000602812.6:n.695+17767C>T

Variant summary

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

The ENST00000602812.6(FTX):​n.695+17767C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 111,139 control chromosomes in the GnomAD database, including 84 homozygotes. There are 657 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 0.023 (84 hom., 657 hem., cov: 22)
• Consequence: FTX ENST00000602812.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

Genes affected

FTX (HGNC:37190): (FTX transcript, XIST regulator) This gene is located upstream of XIST, within the X-inactivation center (XIC). It produces a spliced long non-coding RNA that is thought to positively regulate the expression of XIST, which is essential for the initiation and spread of X-inactivation. [provided by RefSeq, May 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTX	NR_028379.1	n.695+17767C>T		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTX	ENST00000602812.6	n.695+17767C>T		intron_variant	Intron 5 of 6	1
FTX	ENST00000423992.3	n.870+17767C>T		intron_variant	Intron 6 of 6	5
FTX	ENST00000430772.6	n.585+23819C>T		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 2561 AN: 111088 Hom.: 84 Cov.: 22 AF XY: 0.0195 AC XY: 651 AN XY: 33334

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00867

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000381

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00427

Gnomad NFE AF: 0.000226

Gnomad OTH AF: 0.0225

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

GnomAD4 genome AF: 0.0231 AC: 2568 AN: 111139 Hom.: 84 Cov.: 22 AF XY: 0.0197 AC XY: 657 AN XY: 33395

Gnomad4 AFR AF: 0.0796

Gnomad4 AMR AF: 0.00866

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000382

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000226

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0182 Hom.: 50

Bravo AF: 0.0278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs610488; hg19: chrX-73476410;