Genetic Variant CLEC18B:p.Val281Ile (chr16-74412190-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.841G>A(p.Val281Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 37)

Exomes 𝑓: 0.000051 ( 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: -0.430

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=0.041836113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC18B	NM_001385193.1 link	c.841G>A	p.Val281Ile	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.841G>A	p.Val281Ile	missense_variant	Exon 7 of 12		NM_001385193.1	ENSP00000507367.1	A0A804HJ60
CLEC18B	ENST00000339953.9 link	c.841G>A	p.Val281Ile	missense_variant	Exon 7 of 13	1		ENSP00000341051.5	Q6UXF7-1
CLEC18B	ENST00000425714.2 link	n.885G>A		non_coding_transcript_exon_variant	Exon 7 of 7	2
CLEC18B	ENST00000564842.1 link	n.84G>A		non_coding_transcript_exon_variant	Exon 2 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152054

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000505

AC:

AN:

1405682

Hom.:

Cov.:

AF XY:

0.0000545

AC XY:

AN XY:

697632

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000126

Gnomad4 ASJ exome

AF:

0.0000797

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000363

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000559

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000105

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000429

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.841G>A (p.V281I) 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 841, causing the valine (V) at amino acid position 281 to be replaced by an isoleucine (I). 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

0.065

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.027

DANN

Benign

0.89

DEOGEN2

Benign

0.0090

.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.57

T;.;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.042

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

.;.;N;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.050

.;.;N;.

REVEL

Benign

0.013

Sift

Benign

0.42

.;.;T;.

Sift4G

Benign

0.58

T;T;T;T

Polyphen

0.046

.;.;B;.

Vest4

0.069

MVP

0.014

ClinPred

0.037

GERP RS

-4.4

Varity_R

0.025

gMVP

0.062

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