NM_138337.6:c.191-70T>C

Variant names:

• chr12-9979266-T-C
• rs608418
• NM_138337.6:c.191-70T>C

Variant summary

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

The NM_138337.6(CLEC12A):​c.191-70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,226,572 control chromosomes in the GnomAD database, including 179,157 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 (23864 hom., cov: 32)
  • Exomes 𝑓: 0.53 (155293 hom.)
• Consequence: CLEC12A NM_138337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138337.6. 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.191-70T>C		intron	N/A	NP_612210.4
	CLEC12A	NM_001207010.2		c.221-70T>C		intron	N/A	NP_001193939.1	Q5QGZ9-1
	CLEC12A	NM_201623.4		c.92-70T>C		intron	N/A	NP_963917.2	Q5QGZ9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC12A	ENST00000304361.9	TSL:1 MANE Select	c.191-70T>C		intron	N/A	ENSP00000302804.4	Q5QGZ9-2
	CLEC12A	ENST00000355690.8	TSL:1	c.221-70T>C		intron	N/A	ENSP00000347916.4	Q5QGZ9-1
	CLEC12A	ENST00000350667.4	TSL:1	c.92-70T>C		intron	N/A	ENSP00000345448.4	Q5QGZ9-4

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84171 AN: 151910 Hom.: 23843 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.560

GnomAD4 exome AF: 0.529 AC: 568664 AN: 1074544 Hom.: 155293 Cov.: 14 AF XY: 0.536 AC XY: 291414 AN XY: 543626

African (AFR) AF: 0.586 AC: 14094 AN: 24048

American (AMR) AF: 0.590 AC: 16952 AN: 28732

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 11961 AN: 22486

East Asian (EAS) AF: 0.830 AC: 28584 AN: 34434

South Asian (SAS) AF: 0.710 AC: 48866 AN: 68818

European-Finnish (FIN) AF: 0.448 AC: 20761 AN: 46356

Middle Eastern (MID) AF: 0.563 AC: 2433 AN: 4320

European-Non Finnish (NFE) AF: 0.500 AC: 399351 AN: 798622

Other (OTH) AF: 0.549 AC: 25662 AN: 46728

GnomAD4 genome AF: 0.554 AC: 84237 AN: 152028 Hom.: 23864 Cov.: 32 AF XY: 0.558 AC XY: 41469 AN XY: 74316

African (AFR) AF: 0.591 AC: 24475 AN: 41436

American (AMR) AF: 0.576 AC: 8795 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1895 AN: 3472

East Asian (EAS) AF: 0.840 AC: 4348 AN: 5174

South Asian (SAS) AF: 0.745 AC: 3597 AN: 4826

European-Finnish (FIN) AF: 0.439 AC: 4642 AN: 10564

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

European-Non Finnish (NFE) AF: 0.508 AC: 34510 AN: 67964

Other (OTH) AF: 0.565 AC: 1192 AN: 2110

Alfa AF: 0.531 Hom.: 11953

Bravo AF: 0.560

Asia WGS AF: 0.763 AC: 2652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		2.4
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: rs608418; hg19: chr12-10131865; COSMIC: COSV58560838;