Variant 12-53966448-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NR_047517.1(HOTAIR):n.326-71C>T variant causes a intron, non coding transcript 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
NR_047517.1 intron, non_coding_transcript

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.374

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect
HOTAIR	NR_047517.1 linkuse as main transcript	n.326-71C>T	intron_variant, non_coding_transcript_variant
HOTAIR	NR_003716.3 linkuse as main transcript	n.267-71C>T	intron_variant, non_coding_transcript_variant
HOTAIR	NR_047518.1 linkuse as main transcript	n.299-71C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOTAIR	ENST00000424518.5 linkuse as main transcript	n.326-71C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.732

Gnomad4 NFE exome

AF:

0.557

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.575

AC:

87485

AN:

152096

Hom.:

26398

Cov.:

AF XY:

0.581

AC XY:

43234

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.378

Gnomad4 AMR

AF:

0.600

Gnomad4 ASJ

AF:

0.541

Gnomad4 EAS

AF:

0.722

Gnomad4 SAS

AF:

0.585

Gnomad4 FIN

AF:

0.750

Gnomad4 NFE

AF:

0.650

Gnomad4 OTH

AF:

0.585

Alfa

AF:

0.588

Hom.:

3951

Bravo

AF:

0.556

Asia WGS

AF:

0.617

AC:

2143

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.94

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