Genetic Variant CLEC18B:p.Arg133Gln (chr16-74418117-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001385193.1(CLEC18B):c.398G>A(p.Arg133Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,539,516 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 17 hom. )

Consequence

CLEC18B
NM_001385193.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.69

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024249554).

BP6

Variant 16-74418117-C-T is Benign according to our data. Variant chr16-74418117-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2347802.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC18B	NM_001385193.1 link	c.398G>A	p.Arg133Gln	missense_variant	Exon 3 of 12	ENST00000682950.1	NP_001372122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLEC18B	ENST00000682950.1 link	c.398G>A	p.Arg133Gln	missense_variant	Exon 3 of 12		NM_001385193.1	ENSP00000507367.1	A0A804HJ60
CLEC18B	ENST00000339953.9 link	c.398G>A	p.Arg133Gln	missense_variant	Exon 3 of 13	1		ENSP00000341051.5	Q6UXF7-1
CLEC18B	ENST00000425714.2 link	n.416+2384G>A		intron_variant	Intron 2 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.0000997

AC:

AN:

140440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000272

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000228

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.000139

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000223

AC:

AN:

232974

Hom.:

AF XY:

0.000213

AC XY:

AN XY:

126972

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000562

Gnomad ASJ exome

AF:

0.000209

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000280

Gnomad OTH exome

AF:

0.000514

GnomAD4 exome

AF:

0.000179

AC:

250

AN:

1398982

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

130

AN XY:

696872

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000452

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000195

Gnomad4 NFE exome

AF:

0.000203

Gnomad4 OTH exome

AF:

0.000206

GnomAD4 genome

AF:

0.0000996

AC:

AN:

140534

Hom.:

Cov.:

AF XY:

0.0000729

AC XY:

AN XY:

68620

show subpopulations

Gnomad4 AFR

AF:

0.0000271

Gnomad4 AMR

AF:

0.000228

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000139

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000350

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.000229

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 26, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.13

DANN

Benign

0.93

DEOGEN2

Benign

0.0013

.;.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.50

T;.;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.024

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

.;.;N;.

PrimateAI

Benign

0.44

PROVEAN

Benign

0.35

.;.;N;.

REVEL

Benign

0.040

Sift

Benign

0.34

.;.;T;.

Sift4G

Benign

0.31

T;T;T;T

Polyphen

0.0010

.;.;B;.

Vest4

0.13

MVP

0.014

ClinPred

0.036

GERP RS

-6.4

Varity_R

0.028

gMVP

0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over