Genetic Variant HOTAIR:n.961G>A (chr12-53963768-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NR_003716.4(HOTAIR):n.817G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HOTAIR
NR_003716.4 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.75

Variant links:

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]

HOTAIR links:

ENSG00000275589 (HGNC:):

ENSG00000275589 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
HOTAIR	NR_003716.4 link	n.817G>A	non_coding_transcript_exon_variant	Exon 6 of 6
HOTAIR	NR_047517.2 link	n.906G>A	non_coding_transcript_exon_variant	Exon 6 of 6
HOTAIR	NR_047518.2 link	n.634G>A	non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
HOTAIR	ENST00000424518.5 link	n.961G>A	non_coding_transcript_exon_variant	Exon 7 of 7	5
HOTAIR	ENST00000455246.6 link	n.908G>A	non_coding_transcript_exon_variant	Exon 6 of 6	5
HOTAIR	ENST00000425595.5 link	n.*34G>A	downstream_gene_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 NFE exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.57

DANN

Benign

0.93

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over