rs1899663

Positions:

• chr12-53967210-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000439545.1(HOTAIR):​n.299-833G>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 ENST00000439545.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

Genes affected

HOTAIR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HOTAIR	NR_003716.4	n.181+59G>T		intron_variant
HOTAIR	NR_047517.2	n.323+59G>T		intron_variant
HOTAIR	NR_047518.2	n.56-833G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOTAIR	ENST00000424518.5	n.325+59G>T		intron_variant		5
HOTAIR	ENST00000439545.1	n.299-833G>T		intron_variant		4
HOTAIR	ENST00000453875.5	n.87+59G>T		intron_variant		4
HOTAIR	ENST00000455246.6	n.325+59G>T		intron_variant		5

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.208

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

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.298

Alfa AF: 0.305 Hom.: 1861

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1899663; hg19: chr12-54360994;