12-10098846-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016511.4(CLEC1A):c.77G>C(p.Gly26Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,612,902 control chromosomes in the GnomAD database, including 575,530 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54459 hom., cov: 31)

Exomes 𝑓: 0.83 ( 521071 hom. )

Consequence

CLEC1A
NM_016511.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 1.00

Publications

42 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.8313844E-7).

BP6

Variant 12-10098846-C-G is Benign according to our data. Variant chr12-10098846-C-G is described in ClinVar as Benign. ClinVar VariationId is 590287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC1A	NM_016511.4 link	c.77G>C	p.Gly26Ala	missense_variant	Exon 1 of 6	ENST00000315330.8	NP_057595.2	Q8NC01

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC1A	ENST00000315330.8 link	c.77G>C	p.Gly26Ala	missense_variant	Exon 1 of 6	1	NM_016511.4	ENSP00000326407.4		Q8NC01

Frequencies

GnomAD3 genomes

AF:

0.836

AC:

127161

AN:

152036

Hom.:

54423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.898

Gnomad AMI

AF:

0.842

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.874

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.874

Gnomad MID

AF:

0.886

Gnomad NFE

AF:

0.879

Gnomad OTH

AF:

0.826

GnomAD2 exomes

AF:

0.753

AC:

188072

AN:

249870

AF XY:

0.759

show subpopulations

Gnomad AFR exome

AF:

0.897

Gnomad AMR exome

AF:

0.468

Gnomad ASJ exome

AF:

0.875

Gnomad EAS exome

AF:

0.351

Gnomad FIN exome

AF:

0.869

Gnomad NFE exome

AF:

0.883

Gnomad OTH exome

AF:

0.805

GnomAD4 exome

AF:

0.834

AC:

1218965

AN:

1460748

Hom.:

521071

Cov.:

AF XY:

0.830

AC XY:

603306

AN XY:

726576

show subpopulations

African (AFR)

AF:

0.902

AC:

30172

AN:

33462

American (AMR)

AF:

0.496

AC:

22119

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.872

AC:

22782

AN:

26126

East Asian (EAS)

AF:

0.315

AC:

12502

AN:

39648

South Asian (SAS)

AF:

0.634

AC:

54530

AN:

86004

European-Finnish (FIN)

AF:

0.868

AC:

46332

AN:

53364

Middle Eastern (MID)

AF:

0.878

AC:

5066

AN:

5768

European-Non Finnish (NFE)

AF:

0.878

AC:

976091

AN:

1111428

Other (OTH)

AF:

0.818

AC:

49371

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

8780

17559

26339

35118

43898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21060

42120

63180

84240

105300

<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:

0.836

AC:

127241

AN:

152154

Hom.:

54459

Cov.:

AF XY:

0.828

AC XY:

61587

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.898

AC:

37276

AN:

41518

American (AMR)

AF:

0.686

AC:

10478

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.874

AC:

3030

AN:

3468

East Asian (EAS)

AF:

0.347

AC:

1788

AN:

5154

South Asian (SAS)

AF:

0.593

AC:

2858

AN:

4816

European-Finnish (FIN)

AF:

0.874

AC:

9251

AN:

10586

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.879

AC:

59807

AN:

68022

Other (OTH)

AF:

0.819

AC:

1726

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

935

1871

2806

3742

4677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.869

Hom.:

18390

Bravo

AF:

0.824

TwinsUK

AF:

0.876

AC:

3248

ALSPAC

AF:

0.871

AC:

3357

ESP6500AA

AF:

0.899

AC:

3961

ESP6500EA

AF:

0.879

AC:

7560

ExAC

AF:

0.765

AC:

92918

Asia WGS

AF:

0.483

AC:

1682

AN:

3478

EpiCase

AF:

0.878

EpiControl

AF:

0.876

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29489751) -

Aspergillosis, susceptibility to

Other:1

Nov 07, 2018

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.7

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0017

T;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.13

T;T;T;T

MetaRNN

Benign

5.8e-7

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.0

N;.;.;.

PhyloP100

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.95

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;.

Polyphen

0.0

B;B;B;.

Vest4

0.011

MPC

0.038

ClinPred

0.00079

GERP RS

4.7

PromoterAI

0.030

Neutral

(source)

Varity_R

0.028

gMVP

0.17

Mutation Taster

=98/2

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over