rs765021041

Variant names:

• chr16-74411022-C-A
• rs765021041
• NM_001385193.1:c.997G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-74411022-C-A
• chr16-74411022-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385193.1(CLEC18B):​c.997G>T​(p.Val333Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,006 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 59)
  • Exomes 𝑓: 0.000090 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLEC18B NM_001385193.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.806
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20893773).

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.997G>T	p.Val333Leu	missense	Exon 9 of 12	NP_001372122.1	A0A804HJ60
	CLEC18B	NM_001011880.3		c.997G>T	p.Val333Leu	missense	Exon 9 of 13	NP_001011880.2	Q6UXF7-1
	CLEC18B	NM_001385192.1		c.997G>T	p.Val333Leu	missense	Exon 10 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.997G>T	p.Val333Leu	missense	Exon 9 of 12	ENSP00000507367.1	A0A804HJ60
	CLEC18B	ENST00000339953.9	TSL:1	c.997G>T	p.Val333Leu	missense	Exon 9 of 13	ENSP00000341051.5	Q6UXF7-1
	CLEC18B	ENST00000890001.1		c.997G>T	p.Val333Leu	missense	Exon 10 of 13	ENSP00000560060.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152006 Hom.: 0 Cov.: 59

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000609 AC: 15 AN: 246346 AF XY: 0.0000751

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000127

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000902 AC: 131 AN: 1451662 Hom.: 0 Cov.: 128 AF XY: 0.0000928 AC XY: 67 AN XY: 722228

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

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.0000897 AC: 4 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.000154 AC: 4 AN: 25962

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 85920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.000108 AC: 119 AN: 1104800

Other (OTH) AF: 0.0000667 AC: 4 AN: 59960

⚠️ 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 AF: 0.0000132 AC: 2 AN: 152006 Hom.: 0 Cov.: 59 AF XY: 0.0000135 AC XY: 1 AN XY: 74262

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

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67912

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ 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: 0.0000963 Hom.: 0

ExAC AF: 0.000108 AC: 13

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	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N
PhyloP100		0.81
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.064
Sift	Benign	0.040	D
Sift4G	Benign	0.13	T
Polyphen		0.22	B
Vest4		0.20
MutPred		0.58		Loss of MoRF binding (P = 0.0934)
MVP		0.030
ClinPred		0.053	T
GERP RS		0.90
Varity_R		0.068
gMVP		0.18
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs765021041; hg19: chr16-74444920;