Genetic Variant CLEC4E:p.Gly148Asp (chr12-8536135-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014358.4(CLEC4E):c.443G>A(p.Gly148Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,613,578 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G148V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00079 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000078 ( 1 hom. )

Consequence

CLEC4E
NM_014358.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0360

Publications

1 publications found

Variant links:

Genes affected

CLEC4E (HGNC:14555): (C-type lectin domain family 4 member E) 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. The encoded type II transmembrane protein is a downstream target of CCAAT/enhancer binding protein (C/EBP), beta (CEBPB) and may play a role in inflammation. Alternative splice variants have been described but their full-length sequence has not been determined. 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]

CLEC4E links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008160949).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014358.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC4E	NM_014358.4	MANE Select	c.443G>A	p.Gly148Asp	missense	Exon 5 of 6	NP_055173.1	Q9ULY5
	CLEC4E	NM_001410969.1		c.308G>A	p.Gly103Asp	missense	Exon 4 of 5	NP_001397898.1	F5H5X7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC4E	ENST00000299663.8	TSL:1 MANE Select	c.443G>A	p.Gly148Asp	missense	Exon 5 of 6	ENSP00000299663.3	Q9ULY5
CLEC4E	ENST00000545274.5	TSL:3	c.308G>A	p.Gly103Asp	missense	Exon 4 of 5	ENSP00000443034.1	F5H5X7
CLEC4E	ENST00000537698.1	TSL:3	c.189+980G>A		intron	N/A	ENSP00000443328.1	H0YGH9

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000478

GnomAD2 exomes

AF:

0.000243

AC:

AN:

251454

AF XY:

0.000177

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.000231

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:

0.0000780

AC:

114

AN:

1461300

Hom.:

Cov.:

AF XY:

0.0000702

AC XY:

AN XY:

726982

show subpopulations

African (AFR)

AF:

0.00266

AC:

AN:

33456

American (AMR)

AF:

0.000224

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111620

Other (OTH)

AF:

0.000249

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

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:

0.000788

AC:

120

AN:

152278

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00274

AC:

114

AN:

41540

American (AMR)

AF:

0.000327

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000274

Hom.:

Bravo

AF:

0.000956

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000272

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Benign

-0.096

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.20

M_CAP

Benign

0.0073

MetaRNN

Benign

0.0082

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.3

PhyloP100

0.036

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.13

Sift

Benign

0.061

Sift4G

Benign

0.12

Polyphen

0.97

Vest4

0.30

MVP

0.36

MPC

0.17

ClinPred

0.12

GERP RS

3.7

Varity_R

0.20

gMVP

0.62

Mutation Taster

=83/17

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

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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