16-69951476-C-T

Variant names:

• chr16-69951476-C-T
• rs752771955
• NM_001370523.4:c.110C>T

Variant summary

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

The NM_001370523.4(CLEC18A):​c.110C>T​(p.Ala37Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,086 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLEC18A NM_001370523.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.36
• Publications: 0 publications found

Genes affected

CLEC18A (HGNC:30388): (C-type lectin domain family 18 member A) This is one of three closely related paralogous genes on chromosome 16 encoding secreted proteins containing C-type lectin domains. These domains bind to carbohydrates in the presence of calcium, and may be involved in cell adhesion, immune response and apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2012]

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=0.047236145).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370523.4. 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
	CLEC18A	NM_001370523.4	MANE Select	c.110C>T	p.Ala37Val	missense	Exon 1 of 12	NP_001357452.1	A5D8T8-1
	CLEC18A	NM_001136214.4		c.110C>T	p.Ala37Val	missense	Exon 2 of 13	NP_001129686.1	A5D8T8-1
	CLEC18A	NM_001271197.3		c.110C>T	p.Ala37Val	missense	Exon 2 of 13	NP_001258126.1	A5D8T8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC18A	ENST00000288040.11	TSL:1 MANE Select	c.110C>T	p.Ala37Val	missense	Exon 1 of 12	ENSP00000288040.6	A5D8T8-1
	CLEC18A	ENST00000393701.6	TSL:1	c.110C>T	p.Ala37Val	missense	Exon 2 of 13	ENSP00000377304.2	A5D8T8-1
	CLEC18A	ENST00000568461.5	TSL:1	c.110C>T	p.Ala37Val	missense	Exon 2 of 13	ENSP00000454685.1	A5D8T8-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152086 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 248832 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000822 AC: 12 AN: 1459580 Hom.: 0 Cov.: 36 AF XY: 0.00000689 AC XY: 5 AN XY: 726108

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

African (AFR) AF: 0.0000299 AC: 1 AN: 33406

American (AMR) AF: 0.0000671 AC: 3 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111738

Other (OTH) AF: 0.0000166 AC: 1 AN: 60194

⚠️ 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: 0.0000197 AC: 3 AN: 152086 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74288

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

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000359607), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000839 AC: 1

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	0.068
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.9
DANN	Benign	0.92
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.41	N
PhyloP100		-1.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.012
Sift	Benign	0.16	T
Sift4G	Benign	0.18	T
Polyphen		0.0020	B
Vest4		0.018
MutPred		0.25		Loss of disorder (P = 0.0623)
MVP		0.030
MPC		1.9
ClinPred		0.051	T
GERP RS		-5.2
PromoterAI		-0.025	Neutral
Varity_R		0.036
gMVP		0.12
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs752771955; hg19: chr16-69985379;