Genetic Variant NM_001385193.1:c.398G>A (chr16-74418117-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 16/22 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

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2347802.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 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.398G>A	p.Arg133Gln	missense	Exon 3 of 12	NP_001372122.1	A0A804HJ60
CLEC18B	NM_001011880.3		c.398G>A	p.Arg133Gln	missense	Exon 3 of 13	NP_001011880.2	Q6UXF7-1
CLEC18B	NM_001385192.1		c.398G>A	p.Arg133Gln	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.398G>A	p.Arg133Gln	missense	Exon 3 of 12	ENSP00000507367.1	A0A804HJ60
CLEC18B	ENST00000339953.9	TSL:1	c.398G>A	p.Arg133Gln	missense	Exon 3 of 13	ENSP00000341051.5	Q6UXF7-1
CLEC18B	ENST00000890001.1		c.398G>A	p.Arg133Gln	missense	Exon 4 of 13	ENSP00000560060.1

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

GnomAD2 exomes

AF:

0.000223

AC:

AN:

232974

AF XY:

0.000213

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30802

American (AMR)

AF:

0.000452

AC:

AN:

37600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25248

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38868

South Asian (SAS)

AF:

0.00

AC:

AN:

84352

European-Finnish (FIN)

AF:

0.0000195

AC:

AN:

51330

Middle Eastern (MID)

AF:

0.000361

AC:

AN:

5534

European-Non Finnish (NFE)

AF:

0.000203

AC:

217

AN:

1067076

Other (OTH)

AF:

0.000206

AC:

AN:

58172

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.388

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:

0.0000996

AC:

AN:

140534

Hom.:

Cov.:

AF XY:

0.0000729

AC XY:

AN XY:

68620

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000271

AC:

AN:

36834

American (AMR)

AF:

0.000228

AC:

AN:

13144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3292

East Asian (EAS)

AF:

0.00

AC:

AN:

4950

South Asian (SAS)

AF:

0.00

AC:

AN:

4578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10018

Middle Eastern (MID)

AF:

0.00350

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000139

AC:

AN:

64642

Other (OTH)

AF:

0.00

AC:

AN:

1962

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00540043), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.396

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:

0.000350

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.000229

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.068

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.13

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0013

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.50

M_CAP

Benign

0.0070

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

PhyloP100

-1.7

PrimateAI

Benign

0.44

PROVEAN

Benign

0.35

REVEL

Benign

0.040

Sift

Benign

0.34

Sift4G

Benign

0.31

Polyphen

0.0010

Vest4

0.13

MVP

0.014

ClinPred

0.036

GERP RS

-6.4

Varity_R

0.028

gMVP

0.20

Mutation Taster

=98/2

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