rs2092545

chrX-84376466-A-G

Variant summary

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

The NM_001177479.2(HDX):c.1306-14854T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 111,323 control chromosomes in the GnomAD database, including 626 homozygotes. There are 3,641 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 (626 hom., 3641 hem., cov: 23)
• Consequence: HDX NM_001177479.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

Genes affected

HDX (HGNC:26411): (highly divergent homeobox) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDX	NM_001177479.2	c.1306-14854T>C		intron_variant		ENST00000373177.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDX	ENST00000373177.3	c.1306-14854T>C		intron_variant		1	NM_001177479.2	P1
HDX	ENST00000297977.9	c.1306-14854T>C		intron_variant		1		P1
HDX	ENST00000506585.6	c.1132-14854T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 12027 AN: 111272 Hom.: 621 Cov.: 23 AF XY: 0.109 AC XY: 3634 AN XY: 33468

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.0957

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.0940

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

GnomAD4 genome AF: 0.108 AC: 12040 AN: 111323 Hom.: 626 Cov.: 23 AF XY: 0.109 AC XY: 3641 AN XY: 33529

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.0948

Alfa AF: 0.135 Hom.: 2640

Bravo AF: 0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.6
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2092545; hg19: chrX-83631474;