12-8459172-T-C

Position:

• chr12-8459172-T-C

Variant summary

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

The NM_001007033.2(CLEC6A):​c.122-425T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 151,878 control chromosomes in the GnomAD database, including 42,033 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 0.74 (42033 hom., cov: 31)
• Consequence: CLEC6A NM_001007033.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23

Genes affected

CLEC6A (HGNC:14556): (C-type lectin domain containing 6A) The protein encoded by this gene is a type II membrane receptor with an extracellular C-type lectin-like domain fold. The extracellular portion binds structures with a high mannose content and has been shown to recognize several pathogens, including C. elegans, S. cerevisiae, M. tuberculosis, C. neoformans, and house dust mite. When stimulated, the encoded protein initiates signalling through the CARD9-Bcl10-Malt1 pathway, leading to the induction of cytokines. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC6A	NM_001007033.2	c.122-425T>C		intron_variant		ENST00000382073.4	NP_001007034.1
CLEC6A	NM_001317999.2	c.32-425T>C		intron_variant			NP_001304928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC6A	ENST00000382073.4	c.122-425T>C		intron_variant		1	NM_001007033.2	ENSP00000371505.3

Frequencies

GnomAD3 genomes AF: 0.738 AC: 111976 AN: 151760 Hom.: 42015 Cov.: 31

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.738 AC: 112038 AN: 151878 Hom.: 42033 Cov.: 31 AF XY: 0.741 AC XY: 55026 AN XY: 74214

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.806

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.752

Alfa AF: 0.744 Hom.: 4217

Bravo AF: 0.737

Asia WGS AF: 0.876 AC: 3037 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.032
DANN	Benign	0.54

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: rs4264222; hg19: chr12-8611768;