chr12-10129248-A-G

Position:

• chr12-10129248-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.103+732T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,206 control chromosomes in the GnomAD database, including 1,677 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 0.14 (1677 hom., cov: 32)
• Consequence: CLEC7A NM_197947.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC7A	NM_197947.3	c.103+732T>C		intron_variant		ENST00000304084.13	NP_922938.1
LOC105369655	XR_007063208.1	n.182-1833A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC7A	ENST00000304084.13	c.103+732T>C		intron_variant		1	NM_197947.3	ENSP00000302569	P4

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20563 AN: 152088 Hom.: 1677 Cov.: 32

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.00403

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.135 AC: 20566 AN: 152206 Hom.: 1677 Cov.: 32 AF XY: 0.132 AC XY: 9786 AN XY: 74396

Gnomad4 AFR AF: 0.0859

Gnomad4 AMR AF: 0.0865

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.00385

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.118

Alfa AF: 0.166 Hom.: 447

Bravo AF: 0.126

Asia WGS AF: 0.0390 AC: 136 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.81
DANN	Benign	0.86

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: rs7311598; hg19: chr12-10281847;