rs12822416

Variant names:

• chr12-54006444-C-A
• rs12822416
• ENST00000513209.1:c.166+20434C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000513209.1(ENSG00000273049):​c.166+20434C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,284 control chromosomes in the GnomAD database, including 1,452 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 0.13 (1452 hom., cov: 33)
• Consequence: ENSG00000273049 ENST00000513209.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25
• Publications: 6 publications found

Genes affected

ENSG00000273049 (HGNC:):

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000273049	ENST00000513209.1	c.166+20434C>A		intron_variant	Intron 1 of 1	3		ENSP00000476742.1
HOXC6	ENST00000509328.1	c.-73+11428C>A		intron_variant	Intron 1 of 2	3		ENSP00000423898.1
HOXC6	ENST00000504315.1	c.-193+15630C>A		intron_variant	Intron 1 of 1	3		ENSP00000424124.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19366 AN: 152166 Hom.: 1457 Cov.: 33

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0796

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19350 AN: 152284 Hom.: 1452 Cov.: 33 AF XY: 0.125 AC XY: 9287 AN XY: 74470

African (AFR) AF: 0.0553 AC: 2298 AN: 41568

American (AMR) AF: 0.125 AC: 1913 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1151 AN: 5186

South Asian (SAS) AF: 0.228 AC: 1098 AN: 4826

European-Finnish (FIN) AF: 0.0796 AC: 844 AN: 10600

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11052 AN: 68018

Other (OTH) AF: 0.151 AC: 320 AN: 2114

Alfa AF: 0.153 Hom.: 1652

Bravo AF: 0.126

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.91
PhyloP100		3.3

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

Other links and lift over

dbSNP: rs12822416; hg19: chr12-54400228;