rs10840759

Variant names:

• chr12-8138610-C-T
• rs10840759
• ENST00000402465.8:n.113+357C>T

Variant summary

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

The ENST00000402465.8(ENSG00000284393):​n.113+357C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 166,094 control chromosomes in the GnomAD database, including 6,935 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 0.28 (6365 hom., cov: 29)
  • Exomes 𝑓: 0.24 (570 hom.)
• Consequence: ENSG00000284393 ENST00000402465.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594
• Publications: 5 publications found

Genes affected

ENSG00000284393 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000402465.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC4A	NM_016184.4	MANE Select	c.*323C>T		downstream_gene	N/A	NP_057268.1
	CLEC4A	NM_194450.3		c.*323C>T		downstream_gene	N/A	NP_919432.1
	CLEC4A	NM_194447.3		c.*323C>T		downstream_gene	N/A	NP_919429.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000284393	ENST00000402465.8	TSL:2	n.113+357C>T		intron	N/A	ENSP00000384896.4
	CLEC4A	ENST00000229332.12	TSL:1 MANE Select	c.*323C>T		downstream_gene	N/A	ENSP00000229332.5
	CLEC4A	ENST00000345999.9	TSL:5	c.*323C>T		downstream_gene	N/A	ENSP00000344646.3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42041 AN: 149254 Hom.: 6346 Cov.: 29

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.284

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.238 AC: 3999 AN: 16804 Hom.: 570 Cov.: 0 AF XY: 0.236 AC XY: 2034 AN XY: 8602

African (AFR) AF: 0.303 AC: 118 AN: 390

American (AMR) AF: 0.410 AC: 347 AN: 846

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 106 AN: 496

East Asian (EAS) AF: 0.450 AC: 353 AN: 784

South Asian (SAS) AF: 0.273 AC: 333 AN: 1218

European-Finnish (FIN) AF: 0.223 AC: 154 AN: 690

Middle Eastern (MID) AF: 0.269 AC: 21 AN: 78

European-Non Finnish (NFE) AF: 0.206 AC: 2298 AN: 11174

Other (OTH) AF: 0.238 AC: 269 AN: 1128

GnomAD4 genome AF: 0.282 AC: 42079 AN: 149290 Hom.: 6365 Cov.: 29 AF XY: 0.287 AC XY: 20859 AN XY: 72792

African (AFR) AF: 0.332 AC: 13520 AN: 40700

American (AMR) AF: 0.389 AC: 5830 AN: 14980

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 748 AN: 3464

East Asian (EAS) AF: 0.503 AC: 2566 AN: 5106

South Asian (SAS) AF: 0.312 AC: 1482 AN: 4746

European-Finnish (FIN) AF: 0.258 AC: 2466 AN: 9560

Middle Eastern (MID) AF: 0.282 AC: 79 AN: 280

European-Non Finnish (NFE) AF: 0.217 AC: 14660 AN: 67488

Other (OTH) AF: 0.285 AC: 588 AN: 2066

Alfa AF: 0.243 Hom.: 8978

Bravo AF: 0.298

Asia WGS AF: 0.392 AC: 1364 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10840759; hg19: chr12-8291206;