Genetic Variant CLEC18B:p.Arg274Gln (chr16-74412210-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001385193.1(CLEC18B):c.821G>A(p.Arg274Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 37)

Exomes 𝑓: 0.00093 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLEC18B
NM_001385193.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026738644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC18B	NM_001385193.1 link	c.821G>A	p.Arg274Gln	missense_variant	Exon 7 of 12	ENST00000682950.1	NP_001372122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLEC18B	ENST00000682950.1 link	c.821G>A	p.Arg274Gln	missense_variant	Exon 7 of 12		NM_001385193.1	ENSP00000507367.1	A0A804HJ60
CLEC18B	ENST00000339953.9 link	c.821G>A	p.Arg274Gln	missense_variant	Exon 7 of 13	1		ENSP00000341051.5	Q6UXF7-1
CLEC18B	ENST00000425714.2 link	n.865G>A		non_coding_transcript_exon_variant	Exon 7 of 7	2
CLEC18B	ENST00000564842.1 link	n.64G>A		non_coding_transcript_exon_variant	Exon 2 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150988

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00334

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000697

Gnomad OTH

AF:

0.000485

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000932

AC:

1308

AN:

1404062

Hom.:

Cov.:

AF XY:

0.000938

AC XY:

654

AN XY:

697208

show subpopulations

Gnomad4 AFR exome

AF:

0.000216

Gnomad4 AMR exome

AF:

0.000657

Gnomad4 ASJ exome

AF:

0.000237

Gnomad4 EAS exome

AF:

0.0000776

Gnomad4 SAS exome

AF:

0.0000361

Gnomad4 FIN exome

AF:

0.00276

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.000653

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000609

AC:

AN:

151104

Hom.:

Cov.:

AF XY:

0.000759

AC XY:

AN XY:

73804

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.000697

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.00301

Hom.:

ExAC

AF:

0.000133

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.821G>A (p.R274Q) alteration is located in exon 7 (coding exon 7) of the CLEC18B gene. This alteration results from a G to A substitution at nucleotide position 821, causing the arginine (R) at amino acid position 274 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

.;.;T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.46

LIST_S2

Uncertain

0.87

D;.;D;D

MetaRNN

Benign

0.0027

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;.;M;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

.;.;N;.

REVEL

Benign

0.063

Sift

Uncertain

0.0020

.;.;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.61

.;.;P;.

Vest4

0.20

MVP

0.030

ClinPred

0.070

GERP RS

1.2

Varity_R

0.20

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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