12-10123963-A-G

Position:

• chr12-10123963-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_197947.3(CLEC7A):​c.493-600T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,116 control chromosomes in the GnomAD database, including 28,577 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (28577 hom., cov: 32)
• Consequence: CLEC7A NM_197947.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC7A	NM_197947.3	c.493-600T>C		intron_variant		ENST00000304084.13	NP_922938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC7A	ENST00000304084.13	c.493-600T>C		intron_variant		1	NM_197947.3	ENSP00000302569.8

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83948 AN: 152000 Hom.: 28582 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.612

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.552 AC: 83936 AN: 152116 Hom.: 28577 Cov.: 32 AF XY: 0.548 AC XY: 40777 AN XY: 74348

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.603

Alfa AF: 0.719 Hom.: 52624

Bravo AF: 0.522

Asia WGS AF: 0.272 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.76

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: rs2078178; hg19: chr12-10276562;