rs12817092

Positions:

• chr12-53999990-G-A
• chr12-53999990-G-C
• chr12-53999990-G-T

Variant summary

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

The ENST00000513209.1(ENSG00000273049):​c.166+13980G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 608,580 control chromosomes in the GnomAD database, including 94,755 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 0.55 (23257 hom., cov: 29)
  • Exomes 𝑓: 0.56 (71498 hom.)
• Consequence: ENSG00000273049 ENST00000513209.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

ENSG00000273049 (HGNC:):

HOXC9 (HGNC:5130): (homeobox C9) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, which are located on different chromosomes and consist of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXC genes located in a cluster on chromosome 12. [provided by RefSeq, Jul 2008]

HOXC6 (HGNC:5128): (homeobox C6) This gene belongs to the homeobox family, members of which encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, which are located on different chromosomes and consist of 9 to 11 genes arranged in tandem. This gene, HOXC6, is one of several HOXC genes located in a cluster on chromosome 12. Three genes, HOXC5, HOXC4 and HOXC6, share a 5' non-coding exon. Transcripts may include the shared exon spliced to the gene-specific exons, or they may include only the gene-specific exons. Alternatively spliced transcript variants encoding different isoforms have been identified for HOXC6. Transcript variant two includes the shared exon, and transcript variant one includes only gene-specific exons. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXC-AS1	NR_047504.1	n.21C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000273049	ENST00000513209.1	c.166+13980G>A		intron_variant		3		ENSP00000476742.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83416 AN: 150858 Hom.: 23245 Cov.: 29

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.556 AC: 254364 AN: 457604 Hom.: 71498 Cov.: 5 AF XY: 0.551 AC XY: 132535 AN XY: 240490

Gnomad4 AFR exome AF: 0.547

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.543

Gnomad4 EAS exome AF: 0.722

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 0.564

GnomAD4 genome AF: 0.553 AC: 83455 AN: 150976 Hom.: 23257 Cov.: 29 AF XY: 0.549 AC XY: 40484 AN XY: 73744

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.568

Alfa AF: 0.314 Hom.: 527

Asia WGS AF: 0.582 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.3
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12817092; hg19: chr12-54393774;