rs920778

Variant names:

• chr12-53966448-G-A
• rs920778
• ENST00000424518.6:n.324-71C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-53966448-G-A
• chr12-53966448-G-C
• chr12-53966448-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000424518.6(HOTAIR):​n.324-71C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,326 control chromosomes in the GnomAD database, including 26,448 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 0.58 (26398 hom., cov: 33)
  • Exomes 𝑓: 0.65 (50 hom.)
• Consequence: HOTAIR ENST00000424518.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• Publications: 165 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• 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.324-71C>T		intron_variant	Intron 3 of 6	ENST00000424518.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOTAIR	ENST00000424518.6	n.324-71C>T		intron_variant	Intron 3 of 6	5	NR_186241.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87466 AN: 151978 Hom.: 26399 Cov.: 33

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.591

GnomAD4 exome AF: 0.652 AC: 150 AN: 230 Hom.: 50 Cov.: 0 AF XY: 0.623 AC XY: 76 AN XY: 122

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.732 AC: 101 AN: 138

Middle Eastern (MID) AF: 0.500 AC: 4 AN: 8

European-Non Finnish (NFE) AF: 0.557 AC: 39 AN: 70

Other (OTH) AF: 0.500 AC: 4 AN: 8

GnomAD4 genome AF: 0.575 AC: 87485 AN: 152096 Hom.: 26398 Cov.: 33 AF XY: 0.581 AC XY: 43234 AN XY: 74374

African (AFR) AF: 0.378 AC: 15681 AN: 41460

American (AMR) AF: 0.600 AC: 9174 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1875 AN: 3466

East Asian (EAS) AF: 0.722 AC: 3738 AN: 5174

South Asian (SAS) AF: 0.585 AC: 2816 AN: 4816

European-Finnish (FIN) AF: 0.750 AC: 7944 AN: 10588

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44174 AN: 67986

Other (OTH) AF: 0.585 AC: 1231 AN: 2106

Alfa AF: 0.580 Hom.: 3994

Bravo AF: 0.556

Asia WGS AF: 0.617 AC: 2143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.94
PhyloP100		0.37

Splicing

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

Other links and lift over

dbSNP: rs920778; hg19: chr12-54360232;