12-8459172-T-C

Variant names:

• chr12-8459172-T-C
• rs4264222
• NM_001007033.2:c.122-425T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CLEC6A	NM_001007033.2	c.122-425T>C		intron_variant	Intron 2 of 5	ENST00000382073.4	NP_001007034.1
CLEC6A	NM_001317999.2	c.32-425T>C		intron_variant	Intron 1 of 4		NP_001304928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC6A	ENST00000382073.4	c.122-425T>C		intron_variant	Intron 2 of 5	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

African (AFR) AF: 0.595 AC: 24633 AN: 41422

American (AMR) AF: 0.806 AC: 12306 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2519 AN: 3470

East Asian (EAS) AF: 0.988 AC: 5116 AN: 5180

South Asian (SAS) AF: 0.850 AC: 4099 AN: 4820

European-Finnish (FIN) AF: 0.735 AC: 7699 AN: 10478

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53106 AN: 67938

Other (OTH) AF: 0.752 AC: 1583 AN: 2104

Alfa AF: 0.764 Hom.: 12101

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
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4264222; hg19: chr12-8611768;