chr12-10123309-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_197947.3(CLEC7A):c.547C>T(p.Leu183Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,613,528 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0029 ( 23 hom. )

Consequence

CLEC7A
NM_197947.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.90

Publications

17 publications found

Variant links:

Genes affected

CLEC7A (HGNC:14558): (C-type lectin domain containing 7A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with an immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor that recognizes a variety of beta-1,3-linked and beta-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

CLEC7A Gene-Disease associations (from GenCC):

chronic mucocutaneous candidiasis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CLEC7A links:

ENSG00000299754 (HGNC:):

ENSG00000299754 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015158027).

BP6

Variant 12-10123309-G-A is Benign according to our data. Variant chr12-10123309-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 717363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 512 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197947.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC7A	NM_197947.3	MANE Select	c.547C>T	p.Leu183Phe	missense	Exon 5 of 6	NP_922938.1	Q9BXN2-1
CLEC7A	NM_022570.5		c.409C>T	p.Leu137Phe	missense	Exon 4 of 5	NP_072092.2
CLEC7A	NM_197950.3		c.310C>T	p.Leu104Phe	missense	Exon 3 of 4	NP_922941.1	Q9BXN2-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC7A	ENST00000304084.13	TSL:1 MANE Select	c.547C>T	p.Leu183Phe	missense	Exon 5 of 6	ENSP00000302569.8	Q9BXN2-1
CLEC7A	ENST00000353231.9	TSL:1	c.409C>T	p.Leu137Phe	missense	Exon 4 of 5	ENSP00000266456.6	Q9BXN2-2
CLEC7A	ENST00000396484.6	TSL:1	c.310C>T	p.Leu104Phe	missense	Exon 3 of 4	ENSP00000379743.2	Q9BXN2-5

Frequencies

GnomAD3 genomes

AF:

0.00337

AC:

512

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00404

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00369

AC:

928

AN:

251466

AF XY:

0.00376

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00764

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0182

Gnomad NFE exome

AF:

0.00369

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00287

AC:

4194

AN:

1461398

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

2201

AN XY:

727054

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33476

American (AMR)

AF:

0.000157

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00716

AC:

187

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000429

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.0168

AC:

899

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00262

AC:

2908

AN:

1111550

Other (OTH)

AF:

0.00245

AC:

148

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

194

389

583

778

972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.00337

AC:

512

AN:

152130

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

290

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41468

American (AMR)

AF:

0.000392

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0190

AC:

201

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00404

AC:

275

AN:

68012

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

106

132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00379

Hom.:

Bravo

AF:

0.00178

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00367

AC:

446

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00231

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.61

MutationAssessor

Pathogenic

3.5

PhyloP100

1.9

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.28

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.75

MVP

0.37

MPC

0.23

ClinPred

0.13

GERP RS

4.3

Varity_R

0.87

gMVP

0.67

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over