Variant 12-53963768-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
HOTAIR	NR_003716.4 link	n.817G>C	non_coding_transcript_exon_variant	6/6
HOTAIR	NR_047517.2 link	n.906G>C	non_coding_transcript_exon_variant	6/6
HOTAIR	NR_047518.2 link	n.634G>C	non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
HOTAIR	ENST00000424518.5 link	n.961G>C	non_coding_transcript_exon_variant	7/7	5
HOTAIR	ENST00000455246.6 link	n.908G>C	non_coding_transcript_exon_variant	6/6	5
HOTAIR	ENST00000425595.5 link	n.*34G>C	downstream_gene_variant		4

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

Gnomad4 NFE exome

AF:

0.500

GnomAD4 genome

AF:

0.530

AC:

80679

AN:

152110

Hom.:

24278

Cov.:

AF XY:

0.539

AC XY:

40051

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.222

Gnomad4 AMR

AF:

0.584

Gnomad4 ASJ

AF:

0.541

Gnomad4 EAS

AF:

0.723

Gnomad4 SAS

AF:

0.585

Gnomad4 FIN

AF:

0.750

Gnomad4 NFE

AF:

0.650

Gnomad4 OTH

AF:

0.549

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.49

DANN

Benign

0.42

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