12-8533837-A-G

Variant names:

• chr12-8533837-A-G
• rs10841845
• NM_014358.4:c.*801T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
CLEC4E	NM_014358.4	c.*801T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000299663.8	NP_055173.1
CLEC4E	NM_001410969.1	c.*801T>C		3_prime_UTR_variant	Exon 5 of 5		NP_001397898.1
CLEC4E	XM_011520614.4	c.*801T>C		3_prime_UTR_variant	Exon 5 of 5		XP_011518916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC4E	ENST00000299663.8	c.*801T>C		3_prime_UTR_variant	Exon 6 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 4 AN: 8

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.178 AC: 7406 AN: 41516

American (AMR) AF: 0.301 AC: 4605 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2486 AN: 5174

South Asian (SAS) AF: 0.442 AC: 2128 AN: 4810

European-Finnish (FIN) AF: 0.401 AC: 4235 AN: 10572

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21144 AN: 67976

Other (OTH) AF: 0.244 AC: 515 AN: 2114

Alfa AF: 0.298 Hom.: 23628

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
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs10841845; hg19: chr12-8686433;