dbSNP rs10505742: CLEC1B:c.-200-679A>T (chr12-9999979-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000428126.6(CLEC1B):c.-200-679A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,322 control chromosomes in the GnomAD database, including 56 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 0.023 ( 56 hom., cov: 33)

Consequence

CLEC1B
ENST00000428126.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.207

Publications

0 publications found

Variant links:

Genes affected

CLEC1B (HGNC:24356): (C-type lectin domain family 1 member B) Natural killer (NK) cells express multiple calcium-dependent (C-type) lectin-like receptors, such as CD94 (KLRD1; MIM 602894) and NKG2D (KLRC4; MIM 602893), that interact with major histocompatibility complex class I molecules and either inhibit or activate cytotoxicity and cytokine secretion. CLEC2 is a C-type lectin-like receptor expressed in myeloid cells and NK cells (Colonna et al., 2000 [PubMed 10671229]).[supplied by OMIM, Jan 2011]

CLEC1B links:

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=-0.86).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0229 (3483/152322) while in subpopulation NFE AF = 0.0356 (2421/68008). AF 95% confidence interval is 0.0344. There are 56 homozygotes in GnomAd4. There are 1624 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
CLEC1B	NM_001393342.1 link	c.-200-679A>T	intron_variant	Intron 2 of 7	NP_001380271.1
CLEC1B	XM_047428938.1 link	c.-200-679A>T	intron_variant	Intron 2 of 7	XP_047284894.1
CLEC12A	XM_047428402.1 link	c.642-6114T>A	intron_variant	Intron 5 of 5	XP_047284358.1
CLEC1B	XM_011520685.3 link	c.-200-679A>T	intron_variant	Intron 2 of 6	XP_011518987.1	Q9P126-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC1B	ENST00000428126.6 link	c.-200-679A>T		intron_variant	Intron 2 of 6	1		ENSP00000406338.2		Q9P126-2

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3480

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00617

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.0427

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.0222

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0356

Gnomad OTH

AF:

0.0258

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0229

AC:

3483

AN:

152322

Hom.:

Cov.:

AF XY:

0.0218

AC XY:

1624

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00616

AC:

256

AN:

41588

American (AMR)

AF:

0.0169

AC:

258

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0427

AC:

148

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0161

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0222

AC:

236

AN:

10620

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0356

AC:

2421

AN:

68008

Other (OTH)

AF:

0.0255

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

171

342

514

685

856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0307

Hom.:

Bravo

AF:

0.0214

Asia WGS

AF:

0.00954

AC:

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.0

(source)

DANN

Benign

0.74

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over