dbSNP rs1054611: CLEC12B:n.*2309G>T (chr12-10017562-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000539155.1(CLEC12B):n.*2309G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 985,062 control chromosomes in the GnomAD database, including 91,079 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 0.46 ( 16608 hom., cov: 32)

Exomes 𝑓: 0.42 ( 74471 hom. )

Consequence

CLEC12B
ENST00000539155.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.511

Publications

12 publications found

Variant links:

Genes affected

CLEC12B (HGNC:31966): (C-type lectin domain family 12 member B) Enables protein phosphatase binding activity and signaling receptor inhibitor activity. Involved in natural killer cell inhibitory signaling pathway; negative regulation of natural killer cell mediated cytotoxicity; and negative regulation of signaling receptor activity. Located in external side of plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

CLEC12B links:

ENSG00000256803 (HGNC:):

ENSG00000256803 links:

Genome browser will be placed here

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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC12B	NM_001129998.3 link	c.681-769G>T		intron_variant	Intron 5 of 5	ENST00000338896.11	NP_001123470.1	Q2HXU8-1A0A140VK10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC12B	ENST00000338896.11 link	c.681-769G>T		intron_variant	Intron 5 of 5	1	NM_001129998.3	ENSP00000344563.5		Q2HXU8-1

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

69958

AN:

151844

Hom.:

16582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.653

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.404

Gnomad OTH

AF:

0.463

GnomAD4 exome

AF:

0.419

AC:

349330

AN:

833100

Hom.:

74471

Cov.:

AF XY:

0.419

AC XY:

161009

AN XY:

384714

show subpopulations

African (AFR)

AF:

0.498

AC:

7862

AN:

15780

American (AMR)

AF:

0.524

AC:

516

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

2224

AN:

5152

East Asian (EAS)

AF:

0.804

AC:

2920

AN:

3632

South Asian (SAS)

AF:

0.628

AC:

10344

AN:

16460

European-Finnish (FIN)

AF:

0.385

AC:

134

AN:

348

Middle Eastern (MID)

AF:

0.444

AC:

719

AN:

1620

European-Non Finnish (NFE)

AF:

0.409

AC:

311885

AN:

761826

Other (OTH)

AF:

0.466

AC:

12726

AN:

27298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

10608

21216

31824

42432

53040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13264

26528

39792

53056

66320

<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:

0.461

AC:

70024

AN:

151962

Hom.:

16608

Cov.:

AF XY:

0.467

AC XY:

34697

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.497

AC:

20609

AN:

41448

American (AMR)

AF:

0.506

AC:

7716

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

1530

AN:

3470

East Asian (EAS)

AF:

0.800

AC:

4127

AN:

5160

South Asian (SAS)

AF:

0.653

AC:

3142

AN:

4812

European-Finnish (FIN)

AF:

0.368

AC:

3883

AN:

10548

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.404

AC:

27435

AN:

67968

Other (OTH)

AF:

0.470

AC:

993

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1883

3765

5648

7530

9413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.430

Hom.:

12936

Bravo

AF:

0.468

Asia WGS

AF:

0.693

AC:

2411

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

0.45

(source)

DANN

Benign

0.43

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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