rs376806221

Variant names:

• chr16-74418106-C-A
• rs376806221
• NM_001385193.1:c.409G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-74418106-C-A
• chr16-74418106-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001385193.1(CLEC18B):​c.409G>T​(p.Ala137Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A137V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000096 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLEC18B NM_001385193.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.184
• Publications: 1 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=0.055391848).

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.409G>T	p.Ala137Ser	missense	Exon 3 of 12	NP_001372122.1	A0A804HJ60
	CLEC18B	NM_001011880.3		c.409G>T	p.Ala137Ser	missense	Exon 3 of 13	NP_001011880.2	Q6UXF7-1
	CLEC18B	NM_001385192.1		c.409G>T	p.Ala137Ser	missense	Exon 4 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.409G>T	p.Ala137Ser	missense	Exon 3 of 12	ENSP00000507367.1	A0A804HJ60
	CLEC18B	ENST00000339953.9	TSL:1	c.409G>T	p.Ala137Ser	missense	Exon 3 of 13	ENSP00000341051.5	Q6UXF7-1
	CLEC18B	ENST00000890001.1		c.409G>T	p.Ala137Ser	missense	Exon 4 of 13	ENSP00000560060.1

Frequencies

GnomAD3 genomes AF: 0.0000756 AC: 11 AN: 145478 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000284

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000210 AC: 3 AN: 1426732 Hom.: 0 Cov.: 85 AF XY: 0.00000282 AC XY: 2 AN XY: 710038

African (AFR) AF: 0.0000935 AC: 3 AN: 32076

American (AMR) AF: 0.00 AC: 0 AN: 38236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25570

East Asian (EAS) AF: 0.00 AC: 0 AN: 39276

South Asian (SAS) AF: 0.00 AC: 0 AN: 84662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090082

Other (OTH) AF: 0.00 AC: 0 AN: 59222

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000962 AC: 14 AN: 145572 Hom.: 0 Cov.: 33 AF XY: 0.0000703 AC XY: 5 AN XY: 71112

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

African (AFR) AF: 0.000361 AC: 14 AN: 38778

American (AMR) AF: 0.00 AC: 0 AN: 13788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3370

East Asian (EAS) AF: 0.00 AC: 0 AN: 5008

South Asian (SAS) AF: 0.00 AC: 0 AN: 4654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66512

Other (OTH) AF: 0.00 AC: 0 AN: 2012

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000284938), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	0.085
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.1
DANN	Benign	0.88
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.18
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.0060
Sift	Benign	0.55	T
Sift4G	Benign	0.67	T
Polyphen		0.010	B
Vest4		0.18
MutPred		0.34		Gain of disorder (P = 0.0243)
MVP		0.014
ClinPred		0.028	T
GERP RS		-0.10
Varity_R		0.034
gMVP		0.23

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

Other links and lift over

dbSNP: rs376806221; hg19: chr16-74452004;