16-74412210-C-T

Variant names:

• chr16-74412210-C-T
• rs753379322
• NM_001385193.1:c.821G>A

Variant summary

Our verdict is Likely benign. The variant received -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. 13/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026738644).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC18B	NM_001385193.1	MANE Select	c.821G>A	p.Arg274Gln	missense	Exon 7 of 12	NP_001372122.1	A0A804HJ60
	CLEC18B	NM_001011880.3		c.821G>A	p.Arg274Gln	missense	Exon 7 of 13	NP_001011880.2	Q6UXF7-1
	CLEC18B	NM_001385192.1		c.821G>A	p.Arg274Gln	missense	Exon 8 of 13	NP_001372121.1	A0A804HJ60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC18B	ENST00000682950.1	MANE Select	c.821G>A	p.Arg274Gln	missense	Exon 7 of 12	ENSP00000507367.1	A0A804HJ60
	CLEC18B	ENST00000339953.9	TSL:1	c.821G>A	p.Arg274Gln	missense	Exon 7 of 13	ENSP00000341051.5	Q6UXF7-1
	CLEC18B	ENST00000890001.1		c.821G>A	p.Arg274Gln	missense	Exon 8 of 13	ENSP00000560060.1

Frequencies

GnomAD3 genomes AF: 0.000609 AC: 92 AN: 150988 Hom.: 0 Cov.: 37

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

GnomAD2 exomes AF: 0.000757 AC: 59 AN: 77932 AF XY: 0.000766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000756

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00182

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.00160

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000932 AC: 1308 AN: 1404062 Hom.: 0 Cov.: 29 AF XY: 0.000938 AC XY: 654 AN XY: 697208

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

African (AFR) AF: 0.000216 AC: 7 AN: 32450

American (AMR) AF: 0.000657 AC: 26 AN: 39596

Ashkenazi Jewish (ASJ) AF: 0.000237 AC: 6 AN: 25324

East Asian (EAS) AF: 0.0000776 AC: 3 AN: 38662

South Asian (SAS) AF: 0.0000361 AC: 3 AN: 83052

European-Finnish (FIN) AF: 0.00276 AC: 138 AN: 49986

Middle Eastern (MID) AF: 0.000990 AC: 4 AN: 4040

European-Non Finnish (NFE) AF: 0.00101 AC: 1083 AN: 1072774

Other (OTH) AF: 0.000653 AC: 38 AN: 58178

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000609 AC: 92 AN: 151104 Hom.: 0 Cov.: 37 AF XY: 0.000759 AC XY: 56 AN XY: 73804

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

African (AFR) AF: 0.000121 AC: 5 AN: 41448

American (AMR) AF: 0.000197 AC: 3 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00311 AC: 32 AN: 10294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000697 AC: 47 AN: 67410

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00301 Hom.: 0

ExAC AF: 0.000133 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.0
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.063
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.61	P
Vest4		0.20
MVP		0.030
ClinPred		0.070	T
GERP RS		1.2
Varity_R		0.20
gMVP		0.41
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs753379322; hg19: chr16-74446108; COSMIC: COSV60578664;