12-8533837-A-G

Position:

• chr12-8533837-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014358.4(CLEC4E):​c.*801T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,126 control chromosomes in the GnomAD database, including 6,859 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6859 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CLEC4E NM_014358.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC4E	NM_014358.4	c.*801T>C		3_prime_UTR_variant	6/6	ENST00000299663.8	NP_055173.1
CLEC4E	NM_001410969.1	c.*801T>C		3_prime_UTR_variant	5/5		NP_001397898.1
CLEC4E	XM_011520614.4	c.*801T>C		3_prime_UTR_variant	5/5		XP_011518916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC4E	ENST00000299663	c.*801T>C		3_prime_UTR_variant	6/6	1	NM_014358.4	ENSP00000299663.3

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43616 AN: 152002 Hom.: 6860 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.287 AC: 43637 AN: 152118 Hom.: 6859 Cov.: 32 AF XY: 0.294 AC XY: 21834 AN XY: 74346

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.244

Alfa AF: 0.303 Hom.: 14677

Bravo AF: 0.273

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.37

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: rs10841845; hg19: chr12-8686433;