12-53999986-A-G

Variant names:

• chr12-53999986-A-G
• rs56368105
• ENST00000513209.1:c.166+13976A>G

Variant summary

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

The ENST00000513209.1(ENSG00000273049):​c.166+13976A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 604,502 control chromosomes in the GnomAD database, including 52,612 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 0.40 (12104 hom., cov: 29)
  • Exomes 𝑓: 0.42 (40508 hom.)
• Consequence: ENSG00000273049 ENST00000513209.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXC-AS1	NR_047504.1	n.25T>C		non_coding_transcript_exon_variant	Exon 1 of 2
HOXC9	NM_006897.3	c.-203A>G		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+13976A>G		intron_variant	Intron 1 of 1	3		ENSP00000476742.1
HOXC9	ENST00000303450.5	c.-203A>G		upstream_gene_variant		1	NM_006897.3	ENSP00000302836.4

Frequencies

GnomAD3 genomes AF: 0.399 AC: 59906 AN: 150034 Hom.: 12099 Cov.: 29

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.418 AC: 189885 AN: 454352 Hom.: 40508 Cov.: 5 AF XY: 0.412 AC XY: 98607 AN XY: 239172

African (AFR) AF: 0.344 AC: 4141 AN: 12054

American (AMR) AF: 0.409 AC: 6941 AN: 16950

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 5480 AN: 13528

East Asian (EAS) AF: 0.540 AC: 15982 AN: 29578

South Asian (SAS) AF: 0.333 AC: 14178 AN: 42540

European-Finnish (FIN) AF: 0.462 AC: 13392 AN: 29000

Middle Eastern (MID) AF: 0.415 AC: 823 AN: 1982

European-Non Finnish (NFE) AF: 0.418 AC: 118131 AN: 282848

Other (OTH) AF: 0.418 AC: 10817 AN: 25872

GnomAD4 genome AF: 0.399 AC: 59924 AN: 150150 Hom.: 12104 Cov.: 29 AF XY: 0.401 AC XY: 29369 AN XY: 73316

African (AFR) AF: 0.344 AC: 13820 AN: 40212

American (AMR) AF: 0.411 AC: 6249 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1385 AN: 3462

East Asian (EAS) AF: 0.543 AC: 2762 AN: 5082

South Asian (SAS) AF: 0.320 AC: 1531 AN: 4782

European-Finnish (FIN) AF: 0.448 AC: 4679 AN: 10436

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28165 AN: 67702

Other (OTH) AF: 0.407 AC: 850 AN: 2090

Alfa AF: 0.392 Hom.: 1213

Asia WGS AF: 0.368 AC: 1280 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.034
DANN	Benign	0.64
PhyloP100		-0.45
PromoterAI		0.0041	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: rs56368105; hg19: chr12-54393770; COSMIC: COSV100327523; COSMIC: COSV100327523;