12-10125392-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_197947.3(CLEC7A):c.397C>T(p.Leu133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00867 in 1,613,232 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0089 (85 hom.)
• Consequence: CLEC7A NM_197947.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.684

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-10125392-G-A is Benign according to our data. Variant chr12-10125392-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 789214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.684 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC7A	NM_197947.3	c.397C>T	p.Leu133=	synonymous_variant	4/6	ENST00000304084.13
LOC105369655	XR_007063208.1	n.182-5689G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC7A	ENST00000304084.13	c.397C>T	p.Leu133=	synonymous_variant	4/6	1	NM_197947.3	P4

Frequencies

GnomAD3 genomes AF: 0.00629 AC: 956 AN: 152068 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00959

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00724 AC: 1818 AN: 251038 Hom.: 9 AF XY: 0.00761 AC XY: 1033 AN XY: 135714

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0121

Gnomad FIN exome AF: 0.0109

Gnomad NFE exome AF: 0.00936

Gnomad OTH exome AF: 0.00718

GnomAD4 exome AF: 0.00892 AC: 13030 AN: 1461046 Hom.: 85 Cov.: 31 AF XY: 0.00900 AC XY: 6543 AN XY: 726860

Gnomad4 AFR exome AF: 0.00120

Gnomad4 AMR exome AF: 0.00217

Gnomad4 ASJ exome AF: 0.000842

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.00969

Gnomad4 OTH exome AF: 0.00772

GnomAD4 genome AF: 0.00628 AC: 955 AN: 152186 Hom.: 4 Cov.: 32 AF XY: 0.00625 AC XY: 465 AN XY: 74414

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.00249

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.0114

Gnomad4 NFE AF: 0.00959

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00718 Hom.: 3

Bravo AF: 0.00508

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00812

EpiControl AF: 0.00747

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	CLEC7A: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Mar 30, 2018	- -

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

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 07, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	3.9
Dann	Benign	0.67

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: rs144190589; hg19: chr12-10277991; COSMIC: COSV105880501; COSMIC: COSV105880501;