12-10118488-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:4 O:1
• Conservation: PhyloP100: -0.0690

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]

LOC105369655 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• PM4: Stoplost variant in NM_197947.3 Downstream stopcodon found after 25 codons.
• 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	UniProt
CLEC7A	NM_197947.3	c.714T>G	p.Tyr238Ter	stop_gained	6/6	ENST00000304084.13
LOC105369655	XR_007063208.1	n.181+2945A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC7A	ENST00000304084.13	c.714T>G	p.Tyr238Ter	stop_gained	6/6	1	NM_197947.3	P4

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

GnomAD3 exomes AF: 0.0620 AC: 15565 AN: 251140 Hom.: 623 AF XY: 0.0652 AC XY: 8852 AN XY: 135760

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.: 31 AF XY: 0.0761 AC XY: 55160 AN XY: 724786

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.: 32 AF XY: 0.0538 AC XY: 4003 AN XY: 74458

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:1 Benign:4 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial chronic mucocutaneous candidiasis Pathogenic:1 Benign:1

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

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 -

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, criteria provided, single submitter

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	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
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

Other links and lift over

dbSNP: rs16910526; hg19: chr12-10271087; COSMIC: COSV53721870; COSMIC: COSV53721870;