Genetic Variant HOTAIR:n.959G>C (chr12-53963768-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NR_003716.4(HOTAIR):n.817G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,126 control chromosomes in the GnomAD database, including 24,279 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 0.53 ( 24278 hom., cov: 33)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

HOTAIR
NR_003716.4 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.75

Publications

94 publications found

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:

ENSG00000293680 (HGNC:):

ENSG00000293680 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_003716.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
HOTAIR	NR_186241.1	MANE Select	n.959G>C	non_coding_transcript_exon	Exon 7 of 7
HOTAIR	NR_003716.4		n.817G>C	non_coding_transcript_exon	Exon 6 of 6
HOTAIR	NR_047517.2		n.906G>C	non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
HOTAIR	ENST00000424518.6	TSL:5 MANE Select	n.959G>C	non_coding_transcript_exon	Exon 7 of 7
HOTAIR	ENST00000455246.6	TSL:5	n.908G>C	non_coding_transcript_exon	Exon 6 of 6
HOTAIR	ENST00000717836.1		n.713G>C	non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80685

AN:

151992

Hom.:

24284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.754

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.585

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.650

Gnomad OTH

AF:

0.555

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.625

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.530

AC:

80679

AN:

152110

Hom.:

24278

Cov.:

AF XY:

0.539

AC XY:

40051

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.222

AC:

9204

AN:

41502

American (AMR)

AF:

0.584

AC:

8926

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

1876

AN:

3468

East Asian (EAS)

AF:

0.723

AC:

3728

AN:

5154

South Asian (SAS)

AF:

0.585

AC:

2821

AN:

4822

European-Finnish (FIN)

AF:

0.750

AC:

7946

AN:

10594

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.650

AC:

44173

AN:

67966

Other (OTH)

AF:

0.549

AC:

1158

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1665

3330

4996

6661

8326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.456

Hom.:

1521

Bravo

AF:

0.506

Asia WGS

AF:

0.611

AC:

2122

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.49

(source)

DANN

Benign

0.42

PhyloP100

-2.8

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over