rs7302703

Positions:

• chr12-53990603-G-A

Variant summary

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

The 12-53990603-G-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,176 control chromosomes in the GnomAD database, including 6,003 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 0.25 (6002 hom., cov: 31)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: HOXC6 ENST00000504315.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378

Genes affected

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXC6	ENST00000504315.1			upstream_gene_variant		3		ENSP00000424124

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37892 AN: 151974 Hom.: 5986 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.131 AC: 11 AN: 84 Hom.: 1 Cov.: 0 AF XY: 0.155 AC XY: 9 AN XY: 58

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.249 AC: 37942 AN: 152092 Hom.: 6002 Cov.: 31 AF XY: 0.243 AC XY: 18089 AN XY: 74348

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.249

Alfa AF: 0.196 Hom.: 3280

Bravo AF: 0.262

Asia WGS AF: 0.281 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.89

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: rs7302703; hg19: chr12-54384387;