12-10118456-T-C

Variant names:

• chr12-10118456-T-C
• rs7959451
• ENST00000529761.5:n.*2A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000529761.5(CLEC7A):​n.*2A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,604,602 control chromosomes in the GnomAD database, including 539,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51886 hom., cov: 32)
  • Exomes 𝑓: 0.81 (487304 hom.)
• Consequence: CLEC7A ENST00000529761.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.959
• Publications: 26 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 (BayesDel_noAF=-0.91).
• BP6: Variant 12-10118456-T-C is Benign according to our data. Variant chr12-10118456-T-C is described in ClinVar as Benign. ClinVar VariationId is 402543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC7A	NM_197947.3	c.*2A>G		3_prime_UTR_variant	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.*2A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_197947.3	ENSP00000302569.8

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124054 AN: 152042 Hom.: 51852 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.819

GnomAD2 exomes AF: 0.734 AC: 183479 AN: 250088 AF XY: 0.733

Gnomad AFR exome AF: 0.874

Gnomad AMR exome AF: 0.559

Gnomad ASJ exome AF: 0.888

Gnomad EAS exome AF: 0.310

Gnomad FIN exome AF: 0.827

Gnomad NFE exome AF: 0.854

Gnomad OTH exome AF: 0.793

GnomAD4 exome AF: 0.809 AC: 1174451 AN: 1452442 Hom.: 487304 Cov.: 35 AF XY: 0.802 AC XY: 580007 AN XY: 723056

African (AFR) AF: 0.877 AC: 29180 AN: 33256

American (AMR) AF: 0.580 AC: 25790 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 23099 AN: 26060

East Asian (EAS) AF: 0.285 AC: 11267 AN: 39562

South Asian (SAS) AF: 0.543 AC: 46589 AN: 85812

European-Finnish (FIN) AF: 0.832 AC: 44360 AN: 53330

Middle Eastern (MID) AF: 0.864 AC: 4971 AN: 5756

European-Non Finnish (NFE) AF: 0.853 AC: 941375 AN: 1104086

Other (OTH) AF: 0.796 AC: 47820 AN: 60084

GnomAD4 genome AF: 0.816 AC: 124133 AN: 152160 Hom.: 51886 Cov.: 32 AF XY: 0.805 AC XY: 59910 AN XY: 74394

African (AFR) AF: 0.873 AC: 36252 AN: 41510

American (AMR) AF: 0.730 AC: 11147 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3094 AN: 3472

East Asian (EAS) AF: 0.311 AC: 1609 AN: 5176

South Asian (SAS) AF: 0.509 AC: 2455 AN: 4820

European-Finnish (FIN) AF: 0.835 AC: 8835 AN: 10584

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 57980 AN: 68006

Other (OTH) AF: 0.809 AC: 1712 AN: 2116

Alfa AF: 0.834 Hom.: 242097

Bravo AF: 0.811

Asia WGS AF: 0.421 AC: 1465 AN: 3478

EpiCase AF: 0.856

EpiControl AF: 0.852

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.52
PhyloP100		-0.96
Mutation Taster		=100/0	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: rs7959451; hg19: chr12-10271055; COSMIC: COSV53721613; COSMIC: COSV53721613;