12-10018128-A-G

Position:

• chr12-10018128-A-G

Variant summary

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

The NM_001129998.3(CLEC12B):​c.681-203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,112 control chromosomes in the GnomAD database, including 3,127 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 0.19 (3127 hom., cov: 31)
• Consequence: CLEC12B NM_001129998.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

Genes affected

CLEC12B (HGNC:31966): (C-type lectin domain family 12 member B) Enables protein phosphatase binding activity and signaling receptor inhibitor activity. Involved in natural killer cell inhibitory signaling pathway; negative regulation of natural killer cell mediated cytotoxicity; and negative regulation of signaling receptor activity. Located in external side of plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC12B	NM_001129998.3	c.681-203A>G		intron_variant		ENST00000338896.11	NP_001123470.1
LOC102724020	NR_169587.1	n.258-1980T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC12B	ENST00000338896.11	c.681-203A>G		intron_variant		1	NM_001129998.3	ENSP00000344563	P1
CLEC12B	ENST00000544853.5	c.*129-203A>G		intron_variant, NMD_transcript_variant		1		ENSP00000439561
	ENST00000544225.1	n.249-2355T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28887 AN: 151994 Hom.: 3129 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.190 AC: 28882 AN: 152112 Hom.: 3127 Cov.: 31 AF XY: 0.186 AC XY: 13834 AN XY: 74370

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.218

Alfa AF: 0.232 Hom.: 5790

Bravo AF: 0.189

Asia WGS AF: 0.134 AC: 466 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.80

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: rs11053548; hg19: chr12-10170727;