12-10018128-A-G

Variant names:

• chr12-10018128-A-G
• rs11053548
• NM_001129998.3:c.681-203A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ENSG00000256803 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001129998.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC12B	NM_001129998.3	MANE Select	c.681-203A>G		intron	N/A	NP_001123470.1	A0A140VK10
	CLEC12B	NM_001387138.1		c.681-290A>G		intron	N/A	NP_001374067.1
	CLEC12B	NM_001319241.1		c.372-203A>G		intron	N/A	NP_001306170.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC12B	ENST00000338896.11	TSL:1 MANE Select	c.681-203A>G		intron	N/A	ENSP00000344563.5	Q2HXU8-1
	CLEC12B	ENST00000544853.5	TSL:1	n.*129-203A>G		intron	N/A	ENSP00000439561.1	Q2HXU8-2
	ENSG00000256803	ENST00000544225.2	TSL:3	n.301-2355T>C		intron	N/A

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

African (AFR) AF: 0.104 AC: 4330 AN: 41528

American (AMR) AF: 0.161 AC: 2464 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3464

East Asian (EAS) AF: 0.155 AC: 802 AN: 5166

South Asian (SAS) AF: 0.133 AC: 639 AN: 4818

European-Finnish (FIN) AF: 0.161 AC: 1703 AN: 10576

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17343 AN: 67964

Other (OTH) AF: 0.218 AC: 461 AN: 2110

Alfa AF: 0.228 Hom.: 7644

Bravo AF: 0.189

Asia WGS AF: 0.134 AC: 466 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.80
PhyloP100		0.33
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: rs11053548; hg19: chr12-10170727;