Genetic Variant CLEC12A:c.191-70T>C (chr12-9979266-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.45

Publications

14 publications found

Variant links:

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]

CLEC12A links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC12A	NM_138337.6 link	c.191-70T>C		intron_variant	Intron 2 of 5	ENST00000304361.9	NP_612210.4	Q5QGZ9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC12A	ENST00000304361.9 link	c.191-70T>C		intron_variant	Intron 2 of 5	1	NM_138337.6	ENSP00000302804.4		Q5QGZ9-2

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84171

AN:

151910

Hom.:

23843

Cov.:

show subpopulations

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.:

AF XY:

0.536

AC XY:

291414

AN XY:

543626

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

13088

26177

39265

52354

65442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10442

20884

31326

41768

52210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.554

AC:

84237

AN:

152028

Hom.:

23864

Cov.:

AF XY:

0.558

AC XY:

41469

AN XY:

74316

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1887

3774

5660

7547

9434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over