NM_197947.3:c.103+732T>C

Variant names:

• chr12-10129248-A-G
• rs7311598
• NM_197947.3:c.103+732T>C

Variant summary

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

The NM_197947.3(CLEC7A):​c.103+732T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,206 control chromosomes in the GnomAD database, including 1,677 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 0.14 (1677 hom., cov: 32)
• Consequence: CLEC7A NM_197947.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC7A	NM_197947.3	MANE Select	c.103+732T>C		intron	N/A	NP_922938.1
	CLEC7A	NM_022570.5		c.103+732T>C		intron	N/A	NP_072092.2
	CLEC7A	NM_197948.3		c.103+732T>C		intron	N/A	NP_922939.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC7A	ENST00000304084.13	TSL:1 MANE Select	c.103+732T>C		intron	N/A	ENSP00000302569.8
	CLEC7A	ENST00000353231.9	TSL:1	c.103+732T>C		intron	N/A	ENSP00000266456.6
	CLEC7A	ENST00000533022.5	TSL:1	c.103+732T>C		intron	N/A	ENSP00000431461.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20563 AN: 152088 Hom.: 1677 Cov.: 32

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.00403

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.135 AC: 20566 AN: 152206 Hom.: 1677 Cov.: 32 AF XY: 0.132 AC XY: 9786 AN XY: 74396

African (AFR) AF: 0.0859 AC: 3566 AN: 41534

American (AMR) AF: 0.0865 AC: 1322 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 373 AN: 3468

East Asian (EAS) AF: 0.00385 AC: 20 AN: 5194

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4822

European-Finnish (FIN) AF: 0.186 AC: 1970 AN: 10588

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12552 AN: 68004

Other (OTH) AF: 0.118 AC: 249 AN: 2116

Alfa AF: 0.166 Hom.: 447

Bravo AF: 0.126

Asia WGS AF: 0.0390 AC: 136 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.81
DANN	Benign	0.86
PhyloP100		-0.19
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: rs7311598; hg19: chr12-10281847;