12-53971491-T-C

Variant names:

• chr12-53971491-T-C
• rs10783618
• ENST00000424518.6:n.58-2735A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000424518.6(HOTAIR):​n.58-2735A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,204 control chromosomes in the GnomAD database, including 23,790 homozygotes. 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 (23790 hom., cov: 34)
• Consequence: HOTAIR ENST00000424518.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997
• Publications: 18 publications found

Genes affected

HOTAIR (HGNC:33510): (HOX transcript antisense RNA) This gene is located within the Homeobox C (HOXC) gene cluster on chromosome 12 and is co-expressed with the HOXC genes. It functions through an RNA product, which binds lysine specific demethylase 1 (LSD1) and Polycomb repressive complex 2 (PRC2), and serves as a scaffold to assemble these regulators at the HOXD gene cluster, thereby promoting epigenetic repression of HOXD. This gene is highly expressed in multiple tumors. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Feb 2019]

ENSG00000293681 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOTAIR	NR_186241.1	n.58-2735A>G		intron_variant	Intron 1 of 6	ENST00000424518.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOTAIR	ENST00000424518.6	n.58-2735A>G		intron_variant	Intron 1 of 6	5	NR_186241.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78336 AN: 152086 Hom.: 23800 Cov.: 34

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.514 AC: 78308 AN: 152204 Hom.: 23790 Cov.: 34 AF XY: 0.523 AC XY: 38887 AN XY: 74412

African (AFR) AF: 0.169 AC: 7018 AN: 41540

American (AMR) AF: 0.576 AC: 8805 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1874 AN: 3470

East Asian (EAS) AF: 0.722 AC: 3738 AN: 5178

South Asian (SAS) AF: 0.584 AC: 2816 AN: 4820

European-Finnish (FIN) AF: 0.749 AC: 7945 AN: 10602

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44131 AN: 67986

Other (OTH) AF: 0.535 AC: 1133 AN: 2116

Alfa AF: 0.564 Hom.: 11395

Bravo AF: 0.488

Asia WGS AF: 0.601 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs10783618; hg19: chr12-54365275; COSMIC: COSV54533393;