Genetic Variant HOTAIR:n.324-71C>T (chr12-53966448-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.374

Publications

165 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:

ENSG00000293681 (HGNC:):

ENSG00000293681 links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000424518.6. 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.324-71C>T	intron	N/A
HOTAIR	NR_003716.4		n.182-71C>T	intron	N/A
HOTAIR	NR_047517.2		n.324-71C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
HOTAIR	ENST00000424518.6	TSL:5 MANE Select	n.324-71C>T	intron	N/A
HOTAIR	ENST00000710355.2		n.129C>T	non_coding_transcript_exon	Exon 1 of 4
HOTAIR	ENST00000425595.5	TSL:4	n.24-71C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87466

AN:

151978

Hom.:

26399

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.623

AC XY:

AN XY:

122

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.732

AC:

101

AN:

138

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.557

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.575

AC:

87485

AN:

152096

Hom.:

26398

Cov.:

AF XY:

0.581

AC XY:

43234

AN XY:

74374

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1860

3721

5581

7442

9302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<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:

0.580

Hom.:

3994

Bravo

AF:

0.556

Asia WGS

AF:

0.617

AC:

2143

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.37

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