Genetic Variant HOTAIR:n.325+59G>T (chr12-53967210-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000439545.1(HOTAIR):n.299-833G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,012 control chromosomes in the GnomAD database, including 6,235 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 0.28 ( 6234 hom., cov: 31)

Exomes 𝑓: 0.24 ( 1 hom. )

Consequence

HOTAIR
ENST00000439545.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0530

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
HOTAIR	NR_003716.4 link	n.181+59G>T	intron_variant	Intron 2 of 5
HOTAIR	NR_047517.2 link	n.323+59G>T	intron_variant	Intron 3 of 5
HOTAIR	NR_047518.2 link	n.56-833G>T	intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
HOTAIR	ENST00000424518.5 link	n.325+59G>T	intron_variant	Intron 3 of 6	5
HOTAIR	ENST00000439545.1 link	n.299-833G>T	intron_variant	Intron 1 of 3	4
HOTAIR	ENST00000453875.5 link	n.87+59G>T	intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42328

AN:

151860

Hom.:

6219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.294

GnomAD4 exome

AF:

0.235

AC:

AN:

Hom.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.208

GnomAD4 genome

AF:

0.279

AC:

42372

AN:

151978

Hom.:

6234

Cov.:

AF XY:

0.275

AC XY:

20436

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.330

Gnomad4 ASJ

AF:

0.416

Gnomad4 EAS

AF:

0.205

Gnomad4 SAS

AF:

0.322

Gnomad4 FIN

AF:

0.223

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.298

Alfa

AF:

0.305

Hom.:

1861

Bravo

AF:

0.283

Asia WGS

AF:

0.268

AC:

936

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.3

DANN

Benign

0.83

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