rs4759314

chr12-53968051-G-Achr12-53968051-G-Cchr12-53968051-G-T

Variant summary

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

The ENST00000616509.1(ENSG00000274817):n.50G>A 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 0.936 in 152,228 control chromosomes in the GnomAD database, including 67,113 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 0.94 (67087 hom., cov: 31)
  • Exomes 𝑓: 0.98 (26 hom.)
• Consequence: ENST00000616509.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOTAIR	NR_047517.1	n.199+566C>T		intron_variant, non_coding_transcript_variant
HOTAIR	NR_003716.3	n.140+566C>T		intron_variant, non_coding_transcript_variant
HOTAIR	NR_047518.1	n.298+566C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000616509.1	n.50G>A		non_coding_transcript_exon_variant	1/1
HOTAIR	ENST00000424518.5	n.199+566C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142314 AN: 152056 Hom.: 67044 Cov.: 31

Gnomad AFR AF: 0.815

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.956

GnomAD4 exome AF: 0.981 AC: 53 AN: 54 Hom.: 26 Cov.: 0 AF XY: 0.971 AC XY: 33 AN XY: 34

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.936 AC: 142408 AN: 152174 Hom.: 67087 Cov.: 31 AF XY: 0.936 AC XY: 69658 AN XY: 74418

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.971

Gnomad4 ASJ AF: 0.993

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.989

Gnomad4 OTH AF: 0.955

Alfa AF: 0.930 Hom.: 6287

Bravo AF: 0.931

Asia WGS AF: 0.940 AC: 3271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	16
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4759314; hg19: chr12-54361835;