rs369160278

Variant names:

• chr12-10123373-A-G
• rs369160278
• NM_197947.3:c.493-10T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_197947.3(CLEC7A):​c.493-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,344,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: CLEC7A NM_197947.3 intron
• Scores: Splicing: ADA: 0.00005226
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.51
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-10123373-A-G is Benign according to our data. Variant chr12-10123373-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3035819.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 9 AD gene.

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.493-10T>C		intron	N/A	NP_922938.1	Q9BXN2-1
	CLEC7A	NM_022570.5		c.355-10T>C		intron	N/A	NP_072092.2
	CLEC7A	NM_197948.3		c.492+1924T>C		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.493-10T>C		intron	N/A	ENSP00000302569.8	Q9BXN2-1
	CLEC7A	ENST00000353231.9	TSL:1	c.355-10T>C		intron	N/A	ENSP00000266456.6	Q9BXN2-2
	CLEC7A	ENST00000533022.5	TSL:1	c.492+1924T>C		intron	N/A	ENSP00000431461.1	Q9BXN2-3

Frequencies

GnomAD3 genomes AF: 0.0000594 AC: 9 AN: 151398 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000321 AC: 8 AN: 249420 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000499

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000922 AC: 11 AN: 1193372 Hom.: 0 Cov.: 18 AF XY: 0.00000329 AC XY: 2 AN XY: 607414

African (AFR) AF: 0.000352 AC: 10 AN: 28436

American (AMR) AF: 0.00 AC: 0 AN: 44320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24516

East Asian (EAS) AF: 0.00 AC: 0 AN: 38482

South Asian (SAS) AF: 0.00 AC: 0 AN: 80726

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 866794

Other (OTH) AF: 0.00 AC: 0 AN: 51520

GnomAD4 genome AF: 0.0000594 AC: 9 AN: 151398 Hom.: 0 Cov.: 31 AF XY: 0.0000406 AC XY: 3 AN XY: 73924

African (AFR) AF: 0.000220 AC: 9 AN: 40830

American (AMR) AF: 0.00 AC: 0 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000907

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CLEC7A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.58
PhyloP100		2.5

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000052
dbscSNV1_RF	Benign	0.054
SpliceAI score (max)		0.11		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: rs369160278; hg19: chr12-10275972;