16-74418105-G-C

Variant names:

• chr16-74418105-G-C
• rs146242972
• NM_001385193.1:c.410C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001385193.1(CLEC18B):​c.410C>G​(p.Ala137Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 146,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. A137T) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000068 (0 hom., cov: 33)
• Consequence: CLEC18B NM_001385193.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05702007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC18B	NM_001385193.1	c.410C>G	p.Ala137Gly	missense_variant	Exon 3 of 12	ENST00000682950.1	NP_001372122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC18B	ENST00000682950.1	c.410C>G	p.Ala137Gly	missense_variant	Exon 3 of 12		NM_001385193.1	ENSP00000507367.1
CLEC18B	ENST00000339953.9	c.410C>G	p.Ala137Gly	missense_variant	Exon 3 of 13	1		ENSP00000341051.5
CLEC18B	ENST00000425714.2	n.416+2396C>G		intron_variant	Intron 2 of 6	2

Frequencies

GnomAD3 genomes AF: 0.00000684 AC: 1 AN: 146120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 89

GnomAD4 genome AF: 0.00000684 AC: 1 AN: 146120 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 71248

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000150

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.74
DEOGEN2	Benign	0.0027	.;.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.16	T;.;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.057	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.48	.;.;N;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.1	.;.;N;.
REVEL	Benign	0.020
Sift	Benign	0.90	.;.;T;.
Sift4G	Benign	0.70	T;T;T;T
Polyphen		0.0050	.;.;B;.
Vest4		0.17
MutPred		0.36		Gain of catalytic residue at A137 (P = 0.0278);Gain of catalytic residue at A137 (P = 0.0278);Gain of catalytic residue at A137 (P = 0.0278);Gain of catalytic residue at A137 (P = 0.0278);
MVP		0.014
ClinPred		0.019	T
GERP RS		1.4
Varity_R		0.035
gMVP		0.25

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

Other links and lift over

dbSNP: rs146242972; hg19: chr16-74452003;