rs2258287

chr12-121016510-C-Achr12-121016510-C-Gchr12-121016510-C-T

Variant summary

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

The 12-121016510-C-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,611,520 control chromosomes in the GnomAD database, including 102,540 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 (9698 hom., cov: 34)
  • Exomes 𝑓: 0.35 (92842 hom.)
• Consequence: C12orf43 NM_022895.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216

Genes affected

C12orf43 (HGNC:25719): (chromosome 12 open reading frame 43) Predicted to be involved in Spemann organizer formation and negative regulation of Wnt signaling pathway. Predicted to be located in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C12orf43	NM_022895.3			upstream_gene_variant		ENST00000288757.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C12orf43	ENST00000288757.7			upstream_gene_variant		1	NM_022895.3	P2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52540 AN: 152036 Hom.: 9688 Cov.: 34

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.361

GnomAD3 exomes AF: 0.395 AC: 98558 AN: 249496 Hom.: 21334 AF XY: 0.399 AC XY: 53848 AN XY: 134956

Gnomad AFR exome AF: 0.292

Gnomad AMR exome AF: 0.390

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.738

Gnomad SAS exome AF: 0.499

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.380

GnomAD4 exome AF: 0.347 AC: 506015 AN: 1459366 Hom.: 92842 Cov.: 42 AF XY: 0.352 AC XY: 255134 AN XY: 725774

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.720

Gnomad4 SAS exome AF: 0.491

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.377

GnomAD4 genome AF: 0.346 AC: 52581 AN: 152154 Hom.: 9698 Cov.: 34 AF XY: 0.354 AC XY: 26343 AN XY: 74370

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.366

Alfa AF: 0.307 Hom.: 2517

Bravo AF: 0.347

Asia WGS AF: 0.615 AC: 2133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	6.7
Dann	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2258287; hg19: chr12-121454313; COSMIC: COSV105855574;