12-8465967-G-A

Position:

• chr12-8465967-G-A

Variant summary

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

The NM_001007033.2(CLEC6A):​c.369+338G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,142 control chromosomes in the GnomAD database, including 45,949 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 0.77 (45949 hom., cov: 33)
• Consequence: CLEC6A NM_001007033.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707

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=-0.99).
• 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.369+338G>A		intron_variant		ENST00000382073.4	NP_001007034.1
CLEC6A	NM_001317999.2	c.279+338G>A		intron_variant			NP_001304928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC6A	ENST00000382073.4	c.369+338G>A		intron_variant		1	NM_001007033.2	ENSP00000371505	P1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117591 AN: 152024 Hom.: 45926 Cov.: 33

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.773 AC: 117659 AN: 152142 Hom.: 45949 Cov.: 33 AF XY: 0.776 AC XY: 57746 AN XY: 74384

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.834

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.809

Gnomad4 OTH AF: 0.784

Alfa AF: 0.795 Hom.: 5901

Bravo AF: 0.773

Asia WGS AF: 0.897 AC: 3116 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.6
DANN	Benign	0.59

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: rs7134303; hg19: chr12-8618563;