rs1278201907

Variant names:

• chr12-8539295-T-C
• rs1278201907
• NM_014358.4:c.142A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014358.4(CLEC4E):​c.142A>G​(p.Ile48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,608,686 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 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CLEC4E NM_014358.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.323
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040685415).

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.142A>G	p.Ile48Val	missense	Exon 3 of 6	NP_055173.1	Q9ULY5
	CLEC4E	NM_001410969.1		c.142A>G	p.Ile48Val	missense	Exon 3 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.142A>G	p.Ile48Val	missense	Exon 3 of 6	ENSP00000299663.3	Q9ULY5
	CLEC4E	ENST00000545274.5	TSL:3	c.142A>G	p.Ile48Val	missense	Exon 3 of 5	ENSP00000443034.1	F5H5X7
	CLEC4E	ENST00000446457.6	TSL:3	c.142A>G	p.Ile48Val	missense	Exon 3 of 4	ENSP00000387737.2	F8WFA1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247320 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000897

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 AF: 0.00000206 AC: 3 AN: 1456446 Hom.: 0 Cov.: 28 AF XY: 0.00000276 AC XY: 2 AN XY: 724662

African (AFR) AF: 0.00 AC: 0 AN: 33226

American (AMR) AF: 0.0000683 AC: 3 AN: 43954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00 AC: 0 AN: 85434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108924

Other (OTH) AF: 0.00 AC: 0 AN: 60148

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.000589 AC: 9 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	0.080
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.97
DANN	Benign	0.18
DEOGEN2	Benign	0.062	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.32
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.019
Sift	Benign	0.55	T
Sift4G	Benign	0.57	T
Polyphen		0.0040	B
Vest4		0.063
MutPred		0.44		Gain of sheet (P = 0.0827)
MVP		0.085
MPC		0.054
ClinPred		0.042	T
GERP RS		0.040
PromoterAI		-0.013	Neutral
Varity_R		0.028
gMVP		0.11
Mutation Taster		=100/0	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: rs1278201907; hg19: chr12-8691891;