Variant 12-9997193-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016509.4(CLEC1B):c.250G>C(p.Val84Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

CLEC1B
NM_016509.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.114

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:):

CLEC12A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025869638).

BP6

Variant 12-9997193-C-G is Benign according to our data. Variant chr12-9997193-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3267678.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC1B	NM_016509.4 linkuse as main transcript	c.250G>C	p.Val84Leu	missense_variant	3/6	ENST00000298527.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC1B	ENST00000298527.11 linkuse as main transcript	c.250G>C	p.Val84Leu	missense_variant	3/6	1	NM_016509.4	P1	Q9P126-1
CLEC1B	ENST00000348658.4 linkuse as main transcript	c.151G>C	p.Val51Leu	missense_variant	2/5	1			Q9P126-2
CLEC1B	ENST00000428126.6 linkuse as main transcript	c.151G>C	p.Val51Leu	missense_variant	4/7	1			Q9P126-2
CLEC1B	ENST00000398937.6 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000100

AC:

AN:

249458

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000146

AC:

213

AN:

1461712

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

105

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000183

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000138

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.000116

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.097

DANN

Benign

0.52

DEOGEN2

Benign

0.049

.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.57

.;T;T

M_CAP

Benign

0.00086

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.6

.;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.029

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.035

MutPred

0.30

.;Loss of methylation at K86 (P = 0.091);.;

MVP

0.12

MPC

0.044

ClinPred

0.072

GERP RS

-1.7

Varity_R

0.034

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over