rs2092545

Variant names:

• chrX-84376466-A-G
• rs2092545
• NM_001177479.2:c.1306-14854T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HDX	NM_001177479.2	c.1306-14854T>C		intron_variant	Intron 5 of 10	ENST00000373177.3	NP_001170950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDX	ENST00000373177.3	c.1306-14854T>C		intron_variant	Intron 5 of 10	1	NM_001177479.2	ENSP00000362272.2
HDX	ENST00000297977.9	c.1306-14854T>C		intron_variant	Intron 4 of 9	1		ENSP00000297977.5
HDX	ENST00000506585.6	c.1132-14854T>C		intron_variant	Intron 4 of 9	2		ENSP00000423670.2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 12027 AN: 111272 Hom.: 621 Cov.: 23

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

African (AFR) AF: 0.0249 AC: 765 AN: 30765

American (AMR) AF: 0.138 AC: 1451 AN: 10501

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 309 AN: 2636

East Asian (EAS) AF: 0.259 AC: 893 AN: 3453

South Asian (SAS) AF: 0.244 AC: 638 AN: 2616

European-Finnish (FIN) AF: 0.146 AC: 870 AN: 5958

Middle Eastern (MID) AF: 0.0370 AC: 8 AN: 216

European-Non Finnish (NFE) AF: 0.130 AC: 6898 AN: 52990

Other (OTH) AF: 0.0948 AC: 143 AN: 1509

Alfa AF: 0.129 Hom.: 3755

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
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2092545; hg19: chrX-83631474;