chr12-8128312-C-T

Variant names:

• chr12-8128312-C-T
• rs2377422
• NM_016184.4:c.200-952C>T

Variant summary

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

The NM_016184.4(CLEC4A):​c.200-952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,786 control chromosomes in the GnomAD database, including 28,626 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 0.60 (28626 hom., cov: 30)
• Consequence: CLEC4A NM_016184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 14 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]

ENSG00000284697 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016184.4. 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.200-952C>T		intron	N/A	NP_057268.1
	CLEC4A	NM_194450.3		c.199+2635C>T		intron	N/A	NP_919432.1
	CLEC4A	NM_194447.3		c.83-952C>T		intron	N/A	NP_919429.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC4A	ENST00000229332.12	TSL:1 MANE Select	c.200-952C>T		intron	N/A	ENSP00000229332.5
	CLEC4A	ENST00000352620.9	TSL:1	c.199+2635C>T		intron	N/A	ENSP00000247243.5
	CLEC4A	ENST00000360500.5	TSL:5	c.83-952C>T		intron	N/A	ENSP00000353690.3

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91376 AN: 151670 Hom.: 28613 Cov.: 30

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.602 AC: 91435 AN: 151786 Hom.: 28626 Cov.: 30 AF XY: 0.596 AC XY: 44204 AN XY: 74148

African (AFR) AF: 0.443 AC: 18338 AN: 41352

American (AMR) AF: 0.573 AC: 8742 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2609 AN: 3468

East Asian (EAS) AF: 0.442 AC: 2275 AN: 5146

South Asian (SAS) AF: 0.463 AC: 2227 AN: 4814

European-Finnish (FIN) AF: 0.639 AC: 6712 AN: 10500

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.712 AC: 48353 AN: 67936

Other (OTH) AF: 0.635 AC: 1338 AN: 2106

Alfa AF: 0.666 Hom.: 62523

Bravo AF: 0.593

Asia WGS AF: 0.437 AC: 1521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.51
PhyloP100		-0.62
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: rs2377422; hg19: chr12-8280908;