rs4304840

Variant names:

Variant summary

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

The NM_080387.5(CLEC4D):c.94A>G(p.Ser32Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,467,864 control chromosomes in the GnomAD database, including 45,687 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 0.32 ( 9433 hom., cov: 31)

Exomes 𝑓: 0.22 ( 36254 hom. )

Consequence

CLEC4D
NM_080387.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.165

Publications

38 publications found

Variant links:

Genes affected

CLEC4D (HGNC:14554): (C-type lectin domain family 4 member D) 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 signalling, glycoprotein turnover, and roles in inflammation and immune response. 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]

CLEC4D 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=2.259169E-5).

BP6

Variant 12-8515301-A-G is Benign according to our data. Variant chr12-8515301-A-G is described in ClinVar as Benign. ClinVar VariationId is 402542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC4D	NM_080387.5 link	c.94A>G	p.Ser32Gly	missense_variant	Exon 2 of 6	ENST00000299665.3	NP_525126.2	Q8WXI8
CLEC4D	XM_011520632.3 link	c.94A>G	p.Ser32Gly	missense_variant	Exon 3 of 7		XP_011518934.1	Q8WXI8
CLEC4D	XM_047428771.1 link	c.94A>G	p.Ser32Gly	missense_variant	Exon 2 of 6		XP_047284727.1
CLEC4D	XM_047428772.1 link	c.94A>G	p.Ser32Gly	missense_variant	Exon 2 of 6		XP_047284728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC4D	ENST00000299665.3 link	c.94A>G	p.Ser32Gly	missense_variant	Exon 2 of 6	1	NM_080387.5	ENSP00000299665.2		Q8WXI8
CLEC4D	ENST00000382064.6 link	c.94A>G	p.Ser32Gly	missense_variant	Exon 3 of 6	3		ENSP00000371496.2		A6NHA5

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47826

AN:

151746

Hom.:

9414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.563

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.330

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.313

GnomAD2 exomes

AF:

0.234

AC:

58438

AN:

249968

AF XY:

0.233

show subpopulations

Gnomad AFR exome

AF:

0.565

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.273

Gnomad EAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.202

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.222

AC:

292122

AN:

1316000

Hom.:

36254

Cov.:

AF XY:

0.222

AC XY:

147034

AN XY:

662298

show subpopulations

African (AFR)

AF:

0.577

AC:

17264

AN:

29932

American (AMR)

AF:

0.155

AC:

6885

AN:

44392

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

6750

AN:

25092

East Asian (EAS)

AF:

0.127

AC:

4959

AN:

39042

South Asian (SAS)

AF:

0.230

AC:

19099

AN:

83204

European-Finnish (FIN)

AF:

0.208

AC:

10949

AN:

52636

Middle Eastern (MID)

AF:

0.405

AC:

2198

AN:

5426

European-Non Finnish (NFE)

AF:

0.215

AC:

210661

AN:

980860

Other (OTH)

AF:

0.241

AC:

13357

AN:

55416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

8725

17450

26174

34899

43624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6836

13672

20508

27344

34180

<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:

0.315

AC:

47903

AN:

151864

Hom.:

9433

Cov.:

AF XY:

0.313

AC XY:

23227

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.563

AC:

23309

AN:

41388

American (AMR)

AF:

0.221

AC:

3379

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

897

AN:

3468

East Asian (EAS)

AF:

0.141

AC:

730

AN:

5162

South Asian (SAS)

AF:

0.230

AC:

1106

AN:

4812

European-Finnish (FIN)

AF:

0.216

AC:

2281

AN:

10574

Middle Eastern (MID)

AF:

0.328

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.225

AC:

15279

AN:

67892

Other (OTH)

AF:

0.314

AC:

659

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1369

2737

4106

5474

6843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.250

Hom.:

21660

Bravo

AF:

0.327

TwinsUK

AF:

0.214

AC:

793

ALSPAC

AF:

0.217

AC:

835

ESP6500AA

AF:

0.549

AC:

2420

ESP6500EA

AF:

0.231

AC:

1987

ExAC

AF:

0.246

AC:

29918

Asia WGS

AF:

0.209

AC:

726

AN:

3478

EpiCase

AF:

0.237

EpiControl

AF:

0.242

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.14

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.067

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.000023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;L

PhyloP100

-0.17

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.019

Sift

Benign

0.19

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.0030

.;B

Vest4

0.17

MPC

0.029

ClinPred

0.0041

GERP RS

-0.30

Varity_R

0.052

gMVP

0.23

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