12-9983698-C-A

Position:

• chr12-9983698-C-A

Variant summary

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

The ENST00000434319.6(CLEC12A):​c.*168C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 501,424 control chromosomes in the GnomAD database, including 8,813 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 0.16 (2209 hom., cov: 32)
  • Exomes 𝑓: 0.19 (6604 hom.)
• Consequence: CLEC12A ENST00000434319.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

Genes affected

CLEC12A (HGNC:31713): (C-type lectin domain family 12 member A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signaling, glycoprotein turnover, and roles in inflammation and immune response. The protein encoded by this gene is a negative regulator of granulocyte and monocyte function. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. This gene is closely linked to other CTL/CTLD superfamily members in the natural killer gene complex region on chromosome 12p13. [provided by RefSeq, May 2011]

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 (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC12A	NM_138337.6	c.642-1172C>A		intron_variant		ENST00000304361.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC12A	ENST00000304361.9	c.642-1172C>A		intron_variant		1	NM_138337.6	P2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24752 AN: 152030 Hom.: 2203 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.219

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.185 AC: 64622 AN: 349274 Hom.: 6604 Cov.: 0 AF XY: 0.193 AC XY: 35484 AN XY: 184320

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.163 AC: 24773 AN: 152150 Hom.: 2209 Cov.: 32 AF XY: 0.167 AC XY: 12426 AN XY: 74388

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.198

Alfa AF: 0.175 Hom.: 2354

Bravo AF: 0.157

Asia WGS AF: 0.312 AC: 1084 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	7.0
DANN	Benign	0.79

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: rs1323461; hg19: chr12-10136297; COSMIC: COSV58562467; COSMIC: COSV58562467;