12-54023792-C-G

Position:

• chr12-54023792-C-G

Variant summary

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

The NM_014620.6(HOXC4):​c.-124+6378C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,960 control chromosomes in the GnomAD database, including 9,805 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 0.35 (9805 hom., cov: 32)
• Consequence: HOXC4 NM_014620.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

Genes affected

HOXC4 (HGNC:5126): (homeobox C4) 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, HOXC4, is one of several homeobox 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. Two alternatively spliced variants that encode the same protein have been described for HOXC4. Transcript variant one includes the shared exon, and transcript variant two includes only gene-specific exons. [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]

ENSG00000273049 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXC4	NM_014620.6	c.-124+6378C>G		intron_variant			NP_055435.2
HOXC6	NM_153693.5	c.-192-4784C>G		intron_variant			NP_710160.1
HOXC5	NR_003084.3	n.527+6378C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000273049	ENST00000513209.1	c.167-10486C>G		intron_variant		3		ENSP00000476742.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53373 AN: 151842 Hom.: 9796 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.351 AC: 53411 AN: 151960 Hom.: 9805 Cov.: 32 AF XY: 0.358 AC XY: 26593 AN XY: 74282

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.360

Alfa AF: 0.177 Hom.: 394

Bravo AF: 0.341

Asia WGS AF: 0.392 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.54

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: rs736825; hg19: chr12-54417576;