NM_197947.3:c.612-1148G>T

Variant names:

• chr12-10119738-C-A
• rs11053599
• NM_197947.3:c.612-1148G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_197947.3(CLEC7A):​c.612-1148G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 151,852 control chromosomes in the GnomAD database, including 1,810 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 0.13 (1810 hom., cov: 32)
• Consequence: CLEC7A NM_197947.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 4 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 -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 = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC7A	NM_197947.3	c.612-1148G>T		intron_variant	Intron 5 of 5	ENST00000304084.13	NP_922938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC7A	ENST00000304084.13	c.612-1148G>T		intron_variant	Intron 5 of 5	1	NM_197947.3	ENSP00000302569.8

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20077 AN: 151734 Hom.: 1812 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.132 AC: 20070 AN: 151852 Hom.: 1810 Cov.: 32 AF XY: 0.130 AC XY: 9686 AN XY: 74228

African (AFR) AF: 0.0385 AC: 1593 AN: 41418

American (AMR) AF: 0.111 AC: 1695 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3468

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5178

South Asian (SAS) AF: 0.0566 AC: 273 AN: 4824

European-Finnish (FIN) AF: 0.237 AC: 2482 AN: 10466

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13273 AN: 67916

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.174 Hom.: 1325

Bravo AF: 0.119

Asia WGS AF: 0.0380 AC: 132 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	3.2
DANN	Benign	0.76
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11053599; hg19: chr12-10272337;