Genetic Variant CLEC1A:p.Ala42Thr (chr12-10089214-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_016511.4(CLEC1A):c.124G>A(p.Ala42Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,613,744 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 1 hom. )

Consequence

CLEC1A
NM_016511.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.344

Publications

0 publications found

Variant links:

Genes affected

CLEC1A (HGNC:24355): (C-type lectin domain family 1 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 encoded protein may play a role in regulating dendritic cell function. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CLEC1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02559635).

BP6

Variant 12-10089214-C-T is Benign according to our data. Variant chr12-10089214-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2461534.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016511.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CLEC1A	NM_016511.4	MANE Select	c.124G>A	p.Ala42Thr	missense	Exon 2 of 6	NP_057595.2
CLEC1A	NM_001297750.2		c.-141G>A		5_prime_UTR	Exon 3 of 7	NP_001284679.1
CLEC1A	NM_001297751.2		c.-183G>A		5_prime_UTR	Exon 2 of 6	NP_001284680.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC1A	ENST00000315330.8	TSL:1 MANE Select	c.124G>A	p.Ala42Thr	missense	Exon 2 of 6	ENSP00000326407.4	Q8NC01
CLEC1A	ENST00000902292.1		c.124G>A	p.Ala42Thr	missense	Exon 2 of 7	ENSP00000572351.1
CLEC1A	ENST00000414501.2	TSL:4	c.124G>A	p.Ala42Thr	missense	Exon 3 of 3	ENSP00000396272.2	F8WCT4

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

251020

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461474

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727044

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111686

Other (OTH)

AF:

0.000166

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000460

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41552

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.014

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.54

M_CAP

Benign

0.0054

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.36

PhyloP100

0.34

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.4

REVEL

Benign

0.015

Sift

Benign

0.31

Sift4G

Benign

0.78

Polyphen

0.0020

Vest4

0.094

MVP

0.29

MPC

0.036

ClinPred

0.014

GERP RS

-3.6

Varity_R

0.043

gMVP

0.20

Mutation Taster

=96/4

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over