rs16910527

Variant names:

• chr12-10118534-A-C
• rs16910527
• NM_197947.3:c.668T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-10118534-A-C
• chr12-10118534-A-G

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.668T>G​(p.Ile223Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,612,906 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (19 hom.)
• Consequence: CLEC7A NM_197947.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.48
• Publications: 18 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=0.003911674).
• BP6: Variant 12-10118534-A-C is Benign according to our data. Variant chr12-10118534-A-C is described in ClinVar as Benign. ClinVar VariationId is 720451.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 = 0.0102 (1560/152338) while in subpopulation AFR AF = 0.0362 (1504/41566). AF 95% confidence interval is 0.0347. There are 27 homozygotes in GnomAd4. There are 718 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1560 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.668T>G	p.Ile223Ser	missense	Exon 6 of 6	NP_922938.1	Q9BXN2-1
	CLEC7A	NM_022570.5		c.530T>G	p.Ile177Ser	missense	Exon 5 of 5	NP_072092.2
	CLEC7A	NM_197948.3		c.549T>G	p.Asp183Glu	missense	Exon 5 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.668T>G	p.Ile223Ser	missense	Exon 6 of 6	ENSP00000302569.8	Q9BXN2-1
	CLEC7A	ENST00000353231.9	TSL:1	c.530T>G	p.Ile177Ser	missense	Exon 5 of 5	ENSP00000266456.6	Q9BXN2-2
	CLEC7A	ENST00000533022.5	TSL:1	c.549T>G	p.Asp183Glu	missense	Exon 5 of 5	ENSP00000431461.1	Q9BXN2-3

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1558 AN: 152220 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

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: 0.0000735

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00249 AC: 626 AN: 251372 AF XY: 0.00173

Gnomad AFR exome AF: 0.0353

Gnomad AMR exome AF: 0.000839

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000998 AC: 1458 AN: 1460568 Hom.: 19 Cov.: 31 AF XY: 0.000925 AC XY: 672 AN XY: 726704

African (AFR) AF: 0.0342 AC: 1144 AN: 33442

American (AMR) AF: 0.00123 AC: 55 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39664

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5764

European-Non Finnish (NFE) AF: 0.0000702 AC: 78 AN: 1110868

Other (OTH) AF: 0.00255 AC: 154 AN: 60352

GnomAD4 genome AF: 0.0102 AC: 1560 AN: 152338 Hom.: 27 Cov.: 32 AF XY: 0.00964 AC XY: 718 AN XY: 74496

African (AFR) AF: 0.0362 AC: 1504 AN: 41566

American (AMR) AF: 0.00274 AC: 42 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68034

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00457 Hom.: 29

Bravo AF: 0.0111

ESP6500AA AF: 0.0397 AC: 175

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00324 AC: 393

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.5
PROVEAN	Benign	0.48	N
REVEL	Benign	0.087
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.17
MutPred		0.11		Loss of MoRF binding (P = 0.1412)
MVP		0.13
ClinPred		0.030	T
GERP RS		3.8
Varity_R		0.81
Mutation Taster		=98/2	polymorphism

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: rs16910527; hg19: chr12-10271133;