12-53999990-G-A

Variant names:

• chr12-53999990-G-A
• rs12817092
• ENST00000513209.1:c.166+13980G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

Genes affected

ENSG00000273049 (HGNC:):

HOXC-AS1 (HGNC:43749): (HOXC cluster antisense RNA 1)

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HOXC-AS1	NR_047504.1	n.21C>T		non_coding_transcript_exon_variant	Exon 1 of 2
HOXC9	NM_006897.3	c.-199G>A		upstream_gene_variant		ENST00000303450.5	NP_008828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000273049	ENST00000513209.1	c.166+13980G>A		intron_variant	Intron 1 of 1	3		ENSP00000476742.1
HOXC9	ENST00000303450.5	c.-199G>A		upstream_gene_variant		1	NM_006897.3	ENSP00000302836.4

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

African (AFR) AF: 0.547 AC: 6571 AN: 12008

American (AMR) AF: 0.516 AC: 8627 AN: 16728

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 7360 AN: 13556

East Asian (EAS) AF: 0.722 AC: 21199 AN: 29362

South Asian (SAS) AF: 0.499 AC: 21199 AN: 42442

European-Finnish (FIN) AF: 0.515 AC: 15084 AN: 29312

Middle Eastern (MID) AF: 0.558 AC: 1115 AN: 1998

European-Non Finnish (NFE) AF: 0.554 AC: 158547 AN: 286194

Other (OTH) AF: 0.564 AC: 14662 AN: 26004

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

African (AFR) AF: 0.550 AC: 22557 AN: 41020

American (AMR) AF: 0.536 AC: 8158 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1858 AN: 3462

East Asian (EAS) AF: 0.762 AC: 3870 AN: 5076

South Asian (SAS) AF: 0.495 AC: 2364 AN: 4778

European-Finnish (FIN) AF: 0.492 AC: 5135 AN: 10438

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37697 AN: 67696

Other (OTH) AF: 0.568 AC: 1195 AN: 2104

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
PhyloP100		-1.5
PromoterAI		0.047	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs12817092; hg19: chr12-54393774;