12-53991163-A-C

Variant names:

• chr12-53991163-A-C
• rs12304647
• ENST00000513209.1:c.166+5153A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513209.1(ENSG00000273049):​c.166+5153A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,044 control chromosomes in the GnomAD database, including 6,440 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 0.26 (6440 hom., cov: 32)
• Consequence: ENSG00000273049 ENST00000513209.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 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+5153A>C		intron_variant	Intron 1 of 1	3		ENSP00000476742.1
HOXC6	ENST00000504315.1	c.-193+349A>C		intron_variant	Intron 1 of 1	3		ENSP00000424124.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39051 AN: 151924 Hom.: 6423 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.0896

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.257 AC: 39106 AN: 152044 Hom.: 6440 Cov.: 32 AF XY: 0.251 AC XY: 18668 AN XY: 74314

African (AFR) AF: 0.474 AC: 19637 AN: 41444

American (AMR) AF: 0.178 AC: 2724 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3468

East Asian (EAS) AF: 0.223 AC: 1153 AN: 5174

South Asian (SAS) AF: 0.273 AC: 1313 AN: 4816

European-Finnish (FIN) AF: 0.0896 AC: 947 AN: 10574

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12083 AN: 67972

Other (OTH) AF: 0.253 AC: 534 AN: 2110

Alfa AF: 0.198 Hom.: 13035

Bravo AF: 0.270

Asia WGS AF: 0.291 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.85
DANN	Benign	0.47
PhyloP100		-0.35

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: rs12304647; hg19: chr12-54384947;