rs920778

Positions:

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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_047517.1(HOTAIR):​n.326-71C>T variant causes a intron, non coding transcript 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 NR_047517.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HOTAIR	NR_047517.1	n.326-71C>T		intron_variant, non_coding_transcript_variant
HOTAIR	NR_003716.3	n.267-71C>T		intron_variant, non_coding_transcript_variant
HOTAIR	NR_047518.1	n.299-71C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOTAIR	ENST00000424518.5	n.326-71C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.250

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.732

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.585

Alfa AF: 0.588 Hom.: 3951

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs920778; hg19: chr12-54360232;