chr12-9983698-C-A

Variant names:

• chr12-9983698-C-A
• rs1323461
• ENST00000434319.6:c.*168C>A

Variant summary

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

The NM_001300730.2(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 NM_001300730.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300730.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC12A	NM_138337.6	MANE Select	c.642-1172C>A		intron	N/A	NP_612210.4
	CLEC12A	NM_001300730.2		c.*168C>A		3_prime_UTR	Exon 6 of 6	NP_001287659.1	Q5QGZ9-5
	CLEC12A	NM_001207010.2		c.672-1172C>A		intron	N/A	NP_001193939.1	Q5QGZ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC12A	ENST00000434319.6	TSL:1	c.*168C>A		3_prime_UTR	Exon 6 of 6	ENSP00000405244.2	Q5QGZ9-5
	CLEC12A	ENST00000304361.9	TSL:1 MANE Select	c.642-1172C>A		intron	N/A	ENSP00000302804.4	Q5QGZ9-2
	CLEC12A	ENST00000355690.8	TSL:1	c.672-1172C>A		intron	N/A	ENSP00000347916.4	Q5QGZ9-1

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

African (AFR) AF: 0.103 AC: 958 AN: 9346

American (AMR) AF: 0.163 AC: 1880 AN: 11534

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 2967 AN: 11690

East Asian (EAS) AF: 0.182 AC: 4783 AN: 26270

South Asian (SAS) AF: 0.336 AC: 8544 AN: 25412

European-Finnish (FIN) AF: 0.167 AC: 4293 AN: 25732

Middle Eastern (MID) AF: 0.252 AC: 417 AN: 1652

European-Non Finnish (NFE) AF: 0.170 AC: 36768 AN: 216466

Other (OTH) AF: 0.189 AC: 4012 AN: 21172

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

African (AFR) AF: 0.112 AC: 4668 AN: 41528

American (AMR) AF: 0.175 AC: 2673 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 840 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1223 AN: 5178

South Asian (SAS) AF: 0.358 AC: 1721 AN: 4812

European-Finnish (FIN) AF: 0.153 AC: 1620 AN: 10576

Middle Eastern (MID) AF: 0.214 AC: 62 AN: 290

European-Non Finnish (NFE) AF: 0.167 AC: 11335 AN: 67986

Other (OTH) AF: 0.198 AC: 418 AN: 2112

Alfa AF: 0.171 Hom.: 2984

Bravo AF: 0.157

Asia WGS AF: 0.312 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.79
PhyloP100		0.0090
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: rs1323461; hg19: chr12-10136297; COSMIC: COSV58562467; COSMIC: COSV58562467;