chr12-8534732-C-G

Variant names:

• chr12-8534732-C-G
• rs2136396493
• NM_014358.4:c.566G>C

Variant summary

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

The NM_014358.4(CLEC4E):​c.566G>C​(p.Arg189Thr) 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. R189K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLEC4E NM_014358.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 0 publications found

Genes affected

CLEC4E (HGNC:14555): (C-type lectin domain family 4 member E) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type II transmembrane protein is a downstream target of CCAAT/enhancer binding protein (C/EBP), beta (CEBPB) and may play a role in inflammation. Alternative splice variants have been described but their full-length sequence has not been determined. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

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=0.0980522).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014358.4. 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
	CLEC4E	NM_014358.4	MANE Select	c.566G>C	p.Arg189Thr	missense	Exon 6 of 6	NP_055173.1	Q9ULY5
	CLEC4E	NM_001410969.1		c.431G>C	p.Arg144Thr	missense	Exon 5 of 5	NP_001397898.1	F5H5X7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC4E	ENST00000299663.8	TSL:1 MANE Select	c.566G>C	p.Arg189Thr	missense	Exon 6 of 6	ENSP00000299663.3	Q9ULY5
	CLEC4E	ENST00000545274.5	TSL:3	c.431G>C	p.Arg144Thr	missense	Exon 5 of 5	ENSP00000443034.1	F5H5X7
	CLEC4E	ENST00000537698.1	TSL:3	c.267G>C	p.Lys89Asn	missense	Exon 3 of 3	ENSP00000443328.1	H0YGH9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.097	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L
PhyloP100		-0.055
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.040
Sift	Benign	0.094	T
Sift4G	Benign	0.17	T
Polyphen		0.80	P
Vest4		0.21
MutPred		0.48		Loss of solvent accessibility (P = 0.008)
MVP		0.22
MPC		0.31
ClinPred		0.37	T
GERP RS		-0.51
Varity_R		0.15
gMVP		0.54
Mutation Taster		=87/13	polymorphism

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: rs2136396493; hg19: chr12-8687328;