chr12-53966448-G-A

Position:

• chr12-53966448-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000425595.5(HOTAIR):​n.24-71C>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 ENST00000425595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

Genes affected

HOTAIR (HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOTAIR	NR_003716.4	n.182-71C>T		intron_variant
HOTAIR	NR_047517.2	n.324-71C>T		intron_variant
HOTAIR	NR_047518.2	n.56-71C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOTAIR	ENST00000424518.5	n.326-71C>T		intron_variant		5
HOTAIR	ENST00000425595.5	n.24-71C>T		intron_variant		4
HOTAIR	ENST00000439545.1	n.299-71C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87466 AN: 151978 Hom.: 26399 Cov.: 33

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.: 50 Cov.: 0 AF XY: 0.623 AC XY: 76 AN XY: 122

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.: 33 AF XY: 0.581 AC XY: 43234 AN XY: 74374

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	15
DANN	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs920778; hg19: chr12-54360232;