chr12-10125307-G-A

Variant names:

• chr12-10125307-G-A
• rs59819090
• NM_197947.3:c.482C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_197947.3(CLEC7A):​c.482C>T​(p.Ser161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,611,586 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (39 hom.)
• Consequence: CLEC7A NM_197947.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.399
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029134154).
• BP6: Variant 12-10125307-G-A is Benign according to our data. Variant chr12-10125307-G-A is described in ClinVar as Benign. ClinVar VariationId is 376808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0138 (2099/151746) while in subpopulation AFR AF = 0.0467 (1934/41378). AF 95% confidence interval is 0.045. There are 33 homozygotes in GnomAd4. There are 1042 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2099 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.482C>T	p.Ser161Leu	missense	Exon 4 of 6	NP_922938.1	Q9BXN2-1
	CLEC7A	NM_022570.5		c.344C>T	p.Ser115Leu	missense	Exon 3 of 5	NP_072092.2
	CLEC7A	NM_197948.3		c.482C>T	p.Ser161Leu	missense	Exon 4 of 5	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.482C>T	p.Ser161Leu	missense	Exon 4 of 6	ENSP00000302569.8	Q9BXN2-1
	CLEC7A	ENST00000353231.9	TSL:1	c.344C>T	p.Ser115Leu	missense	Exon 3 of 5	ENSP00000266456.6	Q9BXN2-2
	CLEC7A	ENST00000533022.5	TSL:1	c.482C>T	p.Ser161Leu	missense	Exon 4 of 5	ENSP00000431461.1	Q9BXN2-3

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2088 AN: 151630 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00762

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00962

GnomAD2 exomes AF: 0.00369 AC: 928 AN: 251202 AF XY: 0.00274

Gnomad AFR exome AF: 0.0483

Gnomad AMR exome AF: 0.00260

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00160 AC: 2333 AN: 1459840 Hom.: 39 Cov.: 31 AF XY: 0.00137 AC XY: 996 AN XY: 726212

African (AFR) AF: 0.0517 AC: 1729 AN: 33420

American (AMR) AF: 0.00329 AC: 147 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 54 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86236

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 53006

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5756

European-Non Finnish (NFE) AF: 0.000157 AC: 174 AN: 1110840

Other (OTH) AF: 0.00348 AC: 210 AN: 60284

GnomAD4 genome AF: 0.0138 AC: 2099 AN: 151746 Hom.: 33 Cov.: 32 AF XY: 0.0141 AC XY: 1042 AN XY: 74132

African (AFR) AF: 0.0467 AC: 1934 AN: 41378

American (AMR) AF: 0.00761 AC: 116 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10478

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67934

Other (OTH) AF: 0.00952 AC: 20 AN: 2100

Alfa AF: 0.00559 Hom.: 29

Bravo AF: 0.0157

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0472 AC: 208

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00424 AC: 515

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.2
DANN	Benign	0.91
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
PhyloP100		0.40
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.031
Sift	Benign	0.24	T
Sift4G	Benign	0.15	T
Polyphen		0.22	B
Vest4		0.25
MVP		0.29
MPC		0.031
ClinPred		0.0042	T
GERP RS		1.9
Varity_R		0.084
gMVP		0.33
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs59819090; hg19: chr12-10277906;