rs1334854814

Variant names:

• chr16-74412190-C-G
• rs1334854814
• NM_001385193.1:c.841G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-74412190-C-G
• chr16-74412190-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001385193.1(CLEC18B):​c.841G>C​(p.Val281Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V281I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 37)
• Consequence: CLEC18B NM_001385193.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048915).

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.841G>C	p.Val281Leu	missense	Exon 7 of 12	NP_001372122.1	A0A804HJ60
	CLEC18B	NM_001011880.3		c.841G>C	p.Val281Leu	missense	Exon 7 of 13	NP_001011880.2	Q6UXF7-1
	CLEC18B	NM_001385192.1		c.841G>C	p.Val281Leu	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.841G>C	p.Val281Leu	missense	Exon 7 of 12	ENSP00000507367.1	A0A804HJ60
	CLEC18B	ENST00000339953.9	TSL:1	c.841G>C	p.Val281Leu	missense	Exon 7 of 13	ENSP00000341051.5	Q6UXF7-1
	CLEC18B	ENST00000890001.1		c.841G>C	p.Val281Leu	missense	Exon 8 of 13	ENSP00000560060.1

Frequencies

GnomAD3 genomes Cov.: 37

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 37

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0030
DANN	Benign	0.70
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.33	N
PhyloP100		-0.43
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.013
Sift	Benign	0.31	T
Sift4G	Benign	0.43	T
Polyphen		0.0090	B
Vest4		0.11
MutPred		0.36		Gain of catalytic residue at V281 (P = 0.0107)
MVP		0.014
ClinPred		0.10	T
GERP RS		-4.4
Varity_R		0.041
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1334854814; hg19: chr16-74446088;