rs16910526

Variant names:

• chr12-10118488-A-C
• rs16910526
• NM_197947.3:c.714T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-10118488-A-C
• chr12-10118488-A-G
• chr12-10118488-A-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_197947.3(CLEC7A):​c.714T>G​(p.Tyr238*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 1,608,786 control chromosomes in the GnomAD database, including 4,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (309 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4592 hom.)
• Consequence: CLEC7A NM_197947.3 stop_gained
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:5 O:1
• Conservation: PhyloP100: -0.0690
• Publications: 174 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 -16 ACMG points.

• BP6: Variant 12-10118488-A-C is Benign according to our data. Variant chr12-10118488-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 4466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC7A	NM_197947.3	c.714T>G	p.Tyr238*	stop_gained	Exon 6 of 6	ENST00000304084.13	NP_922938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC7A	ENST00000304084.13	c.714T>G	p.Tyr238*	stop_gained	Exon 6 of 6	1	NM_197947.3	ENSP00000302569.8

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8354 AN: 152146 Hom.: 310 Cov.: 32

Gnomad AFR AF: 0.0207

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0881

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0489

GnomAD2 exomes AF: 0.0620 AC: 15565 AN: 251140 AF XY: 0.0652

Gnomad AFR exome AF: 0.0233

Gnomad AMR exome AF: 0.0357

Gnomad ASJ exome AF: 0.0810

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0542

Gnomad NFE exome AF: 0.0764

Gnomad OTH exome AF: 0.0692

GnomAD4 exome AF: 0.0751 AC: 109324 AN: 1456522 Hom.: 4592 Cov.: 31 AF XY: 0.0761 AC XY: 55160 AN XY: 724786

African (AFR) AF: 0.0201 AC: 670 AN: 33394

American (AMR) AF: 0.0367 AC: 1640 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 2120 AN: 26086

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39658

South Asian (SAS) AF: 0.0945 AC: 8141 AN: 86106

European-Finnish (FIN) AF: 0.0571 AC: 3050 AN: 53406

Middle Eastern (MID) AF: 0.0617 AC: 355 AN: 5752

European-Non Finnish (NFE) AF: 0.0804 AC: 89041 AN: 1107252

Other (OTH) AF: 0.0714 AC: 4298 AN: 60198

GnomAD4 genome AF: 0.0549 AC: 8357 AN: 152264 Hom.: 309 Cov.: 32 AF XY: 0.0538 AC XY: 4003 AN XY: 74458

African (AFR) AF: 0.0208 AC: 866 AN: 41562

American (AMR) AF: 0.0467 AC: 715 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.0878 AC: 423 AN: 4818

European-Finnish (FIN) AF: 0.0524 AC: 556 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0771 AC: 5243 AN: 68012

Other (OTH) AF: 0.0479 AC: 101 AN: 2110

Alfa AF: 0.0681 Hom.: 1231

Bravo AF: 0.0530

TwinsUK AF: 0.0887 AC: 329

ALSPAC AF: 0.0745 AC: 287

ESP6500AA AF: 0.0263 AC: 116

ESP6500EA AF: 0.0790 AC: 679

ExAC AF: 0.0631 AC: 7657

Asia WGS AF: 0.0360 AC: 126 AN: 3478

EpiCase AF: 0.0784

EpiControl AF: 0.0773

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1 Benign:5 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial chronic mucocutaneous candidiasis Pathogenic:1 Benign:1

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 09, 2010

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Familial chronic mucocutaneous candidiasis;C3279774:Aspergillosis, susceptibility to Benign:1

Apr 21, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CLEC7A-related disorder Benign:1

May 10, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Aspergillosis, susceptibility to Other:1

Dec 09, 2010

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Uncertain	0.98
Eigen	Benign	-0.082
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.20	N
PhyloP100		-0.069
Vest4		0.34
GERP RS		-2.3
Mutation Taster		=181/19	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: rs16910526; hg19: chr12-10271087; COSMIC: COSV53721870; COSMIC: COSV53721870;