chr12-53967210-C-A

Variant names:

• chr12-53967210-C-A
• rs1899663
• ENST00000424518.6:n.323+59G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000424518.6(HOTAIR):​n.323+59G>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 ENST00000424518.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 116 publications found

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]

ENSG00000293681 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOTAIR	NR_003716.4	n.181+59G>T		intron_variant	Intron 2 of 5
HOTAIR	NR_047517.2	n.323+59G>T		intron_variant	Intron 3 of 5
HOTAIR	NR_047518.2	n.56-833G>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOTAIR	ENST00000424518.6	n.323+59G>T		intron_variant	Intron 3 of 6	5
HOTAIR	ENST00000439545.1	n.299-833G>T		intron_variant	Intron 1 of 3	4
HOTAIR	ENST00000453875.5	n.87+59G>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42328 AN: 151860 Hom.: 6219 Cov.: 31

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: 8 AN: 34 Hom.: 1 AF XY: 0.125 AC XY: 2 AN XY: 16

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.208 AC: 5 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.279 AC: 42372 AN: 151978 Hom.: 6234 Cov.: 31 AF XY: 0.275 AC XY: 20436 AN XY: 74274

African (AFR) AF: 0.199 AC: 8242 AN: 41430

American (AMR) AF: 0.330 AC: 5050 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1442 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1054 AN: 5154

South Asian (SAS) AF: 0.322 AC: 1548 AN: 4810

European-Finnish (FIN) AF: 0.223 AC: 2358 AN: 10564

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21726 AN: 67946

Other (OTH) AF: 0.298 AC: 629 AN: 2114

Alfa AF: 0.299 Hom.: 2892

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
PhyloP100		-0.053

Splicing

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

Other links and lift over

dbSNP: rs1899663; hg19: chr12-54360994;