12-8138526-T-G

Variant names:

• chr12-8138526-T-G
• rs1133104
• NM_016184.4:c.*239T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016184.4(CLEC4A):​c.*239T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 408,270 control chromosomes in the GnomAD database, including 12,558 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 0.25 (5164 hom., cov: 30)
  • Exomes 𝑓: 0.23 (7394 hom.)
• Consequence: CLEC4A NM_016184.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.868
• Publications: 13 publications found

Genes affected

CLEC4A (HGNC:13257): (C-type lectin domain family 4 member A) 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 2 transmembrane protein may play a role in inflammatory and immune response. Multiple transcript variants encoding distinct isoforms have been identified for this gene. 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]

ENSG00000284393 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC4A	NM_016184.4	c.*239T>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000229332.12	NP_057268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC4A	ENST00000229332.12	c.*239T>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_016184.4	ENSP00000229332.5
ENSG00000284393	ENST00000402465.8	n.113+273T>G		intron_variant	Intron 1 of 4	2		ENSP00000384896.4

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38256 AN: 151632 Hom.: 5156 Cov.: 30

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.232 AC: 59448 AN: 256524 Hom.: 7394 Cov.: 3 AF XY: 0.231 AC XY: 30724 AN XY: 132902

African (AFR) AF: 0.243 AC: 1685 AN: 6944

American (AMR) AF: 0.424 AC: 3543 AN: 8352

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 2131 AN: 8744

East Asian (EAS) AF: 0.0868 AC: 1604 AN: 18480

South Asian (SAS) AF: 0.186 AC: 3281 AN: 17620

European-Finnish (FIN) AF: 0.246 AC: 4310 AN: 17552

Middle Eastern (MID) AF: 0.256 AC: 325 AN: 1272

European-Non Finnish (NFE) AF: 0.239 AC: 38607 AN: 161246

Other (OTH) AF: 0.243 AC: 3962 AN: 16314

GnomAD4 genome AF: 0.252 AC: 38290 AN: 151746 Hom.: 5164 Cov.: 30 AF XY: 0.253 AC XY: 18781 AN XY: 74168

African (AFR) AF: 0.244 AC: 10079 AN: 41350

American (AMR) AF: 0.391 AC: 5960 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3468

East Asian (EAS) AF: 0.107 AC: 553 AN: 5172

South Asian (SAS) AF: 0.193 AC: 928 AN: 4818

European-Finnish (FIN) AF: 0.260 AC: 2735 AN: 10502

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.241 AC: 16396 AN: 67894

Other (OTH) AF: 0.252 AC: 529 AN: 2100

Alfa AF: 0.253 Hom.: 8671

Bravo AF: 0.265

Asia WGS AF: 0.152 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.85
PhyloP100		0.87
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: rs1133104; hg19: chr12-8291122;