Genetic Variant CLEC18B:p.Ala137Thr (chr16-74418106-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001385193.1(CLEC18B):c.409G>A(p.Ala137Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000356 in 1,572,220 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A137S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 5 hom. )

Consequence

CLEC18B
NM_001385193.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.184

Publications

1 publications found

Variant links:

Genes affected

CLEC18B (HGNC:33849): (C-type lectin domain family 18 member B) Predicted to enable polysaccharide binding activity. Predicted to be located in Golgi apparatus; endosome; and sarcoplasmic reticulum. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

CLEC18B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029900879).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385193.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC18B	NM_001385193.1	MANE Select	c.409G>A	p.Ala137Thr	missense	Exon 3 of 12	NP_001372122.1	A0A804HJ60
CLEC18B	NM_001011880.3		c.409G>A	p.Ala137Thr	missense	Exon 3 of 13	NP_001011880.2	Q6UXF7-1
CLEC18B	NM_001385192.1		c.409G>A	p.Ala137Thr	missense	Exon 4 of 13	NP_001372121.1	A0A804HJ60

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC18B	ENST00000682950.1	MANE Select	c.409G>A	p.Ala137Thr	missense	Exon 3 of 12	ENSP00000507367.1	A0A804HJ60
CLEC18B	ENST00000339953.9	TSL:1	c.409G>A	p.Ala137Thr	missense	Exon 3 of 13	ENSP00000341051.5	Q6UXF7-1
CLEC18B	ENST00000890001.1		c.409G>A	p.Ala137Thr	missense	Exon 4 of 13	ENSP00000560060.1

Frequencies

GnomAD3 genomes

AF:

0.0000344

AC:

AN:

145492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000593

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000301

Gnomad OTH

AF:

0.000503

GnomAD2 exomes

AF:

0.0000693

AC:

AN:

230760

AF XY:

0.0000556

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00158

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000945

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000357

AC:

AN:

1426728

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

710042

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32080

American (AMR)

AF:

0.00

AC:

AN:

38234

Ashkenazi Jewish (ASJ)

AF:

0.00125

AC:

AN:

25570

East Asian (EAS)

AF:

0.00

AC:

AN:

39276

South Asian (SAS)

AF:

0.0000236

AC:

AN:

84662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52080

Middle Eastern (MID)

AF:

0.000181

AC:

AN:

5528

European-Non Finnish (NFE)

AF:

0.0000119

AC:

AN:

1090076

Other (OTH)

AF:

0.0000507

AC:

AN:

59222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.0000344

AC:

AN:

145492

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

71004

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38684

American (AMR)

AF:

0.00

AC:

AN:

13780

Ashkenazi Jewish (ASJ)

AF:

0.000593

AC:

AN:

3370

East Asian (EAS)

AF:

0.00

AC:

AN:

5018

South Asian (SAS)

AF:

0.00

AC:

AN:

4658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000301

AC:

AN:

66520

Other (OTH)

AF:

0.000503

AC:

AN:

1990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000194

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.0000972

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.071

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.4

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0079

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.15

M_CAP

Benign

0.0064

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.18

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.2

REVEL

Benign

0.0070

Sift

Benign

0.15

Sift4G

Benign

0.39

Polyphen

0.66

Vest4

0.20

MVP

0.014

ClinPred

0.016

GERP RS

-0.10

Varity_R

0.031

gMVP

0.25

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over