Variant chr12-9995251-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016509.4(CLEC1B):c.439-5A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,606,662 control chromosomes in the GnomAD database, including 60,491 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7140 hom., cov: 32)

Exomes 𝑓: 0.27 ( 53351 hom. )

Consequence

CLEC1B
NM_016509.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0005377

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.610

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 made for transcript

Verdict is Benign. Variant got -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 = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC1B	NM_016509.4 linkuse as main transcript	c.439-5A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000298527.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC1B	ENST00000298527.11 linkuse as main transcript	c.439-5A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_016509.4	P1	Q9P126-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45153

AN:

151914

Hom.:

7120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.276

AC:

68702

AN:

248558

Hom.:

10263

AF XY:

0.287

AC XY:

38724

AN XY:

134894

show subpopulations

Gnomad AFR exome

AF:

0.407

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.242

Gnomad SAS exome

AF:

0.406

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.285

GnomAD4 exome

AF:

0.266

AC:

386887

AN:

1454628

Hom.:

53351

Cov.:

AF XY:

0.271

AC XY:

196399

AN XY:

724050

show subpopulations

Gnomad4 AFR exome

AF:

0.394

Gnomad4 AMR exome

AF:

0.175

Gnomad4 ASJ exome

AF:

0.330

Gnomad4 EAS exome

AF:

0.211

Gnomad4 SAS exome

AF:

0.401

Gnomad4 FIN exome

AF:

0.237

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.297

AC:

45217

AN:

152034

Hom.:

7140

Cov.:

AF XY:

0.298

AC XY:

22138

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.398

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.317

Gnomad4 EAS

AF:

0.235

Gnomad4 SAS

AF:

0.421

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.272

Hom.:

13103

Bravo

AF:

0.298

Asia WGS

AF:

0.347

AC:

1207

AN:

3478

EpiCase

AF:

0.270

EpiControl

AF:

0.283

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.5

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00054

dbscSNV1_RF

Benign

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over