12-10128656-C-T

Variant names:

• chr12-10128656-C-T
• rs16910631
• NM_197947.3:c.104-811G>A

Variant summary

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

The NM_197947.3(CLEC7A):​c.104-811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 152,078 control chromosomes in the GnomAD database, including 265 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 0.053 (265 hom., cov: 32)
• Consequence: CLEC7A NM_197947.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672
• Publications: 11 publications found

Genes affected

CLEC7A (HGNC:14558): (C-type lectin domain containing 7A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with an immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor that recognizes a variety of beta-1,3-linked and beta-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. 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]

CLEC7A Gene-Disease associations (from GenCC):

• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000299754 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197947.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC7A	NM_197947.3	MANE Select	c.104-811G>A		intron	N/A	NP_922938.1	Q9BXN2-1
	CLEC7A	NM_022570.5		c.104-811G>A		intron	N/A	NP_072092.2
	CLEC7A	NM_197948.3		c.104-811G>A		intron	N/A	NP_922939.1	Q9BXN2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC7A	ENST00000304084.13	TSL:1 MANE Select	c.104-811G>A		intron	N/A	ENSP00000302569.8	Q9BXN2-1
	CLEC7A	ENST00000353231.9	TSL:1	c.104-811G>A		intron	N/A	ENSP00000266456.6	Q9BXN2-2
	CLEC7A	ENST00000533022.5	TSL:1	c.104-811G>A		intron	N/A	ENSP00000431461.1	Q9BXN2-3

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 8053 AN: 151960 Hom.: 263 Cov.: 32

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.0542

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

GnomAD4 genome AF: 0.0530 AC: 8058 AN: 152078 Hom.: 265 Cov.: 32 AF XY: 0.0513 AC XY: 3815 AN XY: 74342

African (AFR) AF: 0.0373 AC: 1549 AN: 41480

American (AMR) AF: 0.0464 AC: 709 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3468

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5178

South Asian (SAS) AF: 0.0533 AC: 257 AN: 4824

European-Finnish (FIN) AF: 0.0311 AC: 328 AN: 10544

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0690 AC: 4693 AN: 67994

Other (OTH) AF: 0.0532 AC: 112 AN: 2106

Alfa AF: 0.0646 Hom.: 563

Bravo AF: 0.0541

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.79
PhyloP100		-0.67
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: rs16910631; hg19: chr12-10281255;