rs16910526

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_197947.3(CLEC7A):c.714T>G(p.Tyr238Ter) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:5O:1

Conservation

PhyloP100: -0.0690

Variant links:

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 links:

LOC105369655 (HGNC:):

LOC105369655 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 4466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-10118488-A-C is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
CLEC7A	NM_197947.3 linkuse as main transcript	c.714T>G	p.Tyr238Ter	stop_gained	6/6	ENST00000304084.13	NP_922938.1
LOC105369655	XR_007063208.1 linkuse as main transcript	n.181+2945A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC7A	ENST00000304084.13 linkuse as main transcript	c.714T>G	p.Tyr238Ter	stop_gained	6/6	1	NM_197947.3	ENSP00000302569	P4	Q9BXN2-1

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8354

AN:

152146

Hom.:

310

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0620

AC:

15565

AN:

251140

Hom.:

623

AF XY:

0.0652

AC XY:

8852

AN XY:

135760

show subpopulations

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 SAS exome

AF:

0.0935

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.:

AF XY:

0.0761

AC XY:

55160

AN XY:

724786

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.0367

Gnomad4 ASJ exome

AF:

0.0813

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0945

Gnomad4 FIN exome

AF:

0.0571

Gnomad4 NFE exome

AF:

0.0804

Gnomad4 OTH exome

AF:

0.0714

GnomAD4 genome

AF:

0.0549

AC:

8357

AN:

152264

Hom.:

309

Cov.:

AF XY:

0.0538

AC XY:

4003

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0208

Gnomad4 AMR

AF:

0.0467

Gnomad4 ASJ

AF:

0.0784

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0878

Gnomad4 FIN

AF:

0.0524

Gnomad4 NFE

AF:

0.0771

Gnomad4 OTH

AF:

0.0479

Alfa

AF:

0.0708

Hom.:

868

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:1Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial chronic mucocutaneous candidiasis

Pathogenic:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Dec 09, 2010	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Familial chronic mucocutaneous candidiasis;C3279774:Aspergillosis, susceptibility to

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 21, 2022

- -

CLEC7A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 10, 2022

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

risk factor, no assertion criteria provided

literature only

OMIM

Dec 09, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Benign

-0.082

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.20

MutationTaster

Benign

1.0

A;A;A;A;A

Vest4

0.34

GERP RS

-2.3

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over