chr12-9990298-G-A

Position:

• chr12-9990298-G-A

Variant summary

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

The ENST00000398937.6(CLEC1B):​c.267-4140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,052 control chromosomes in the GnomAD database, including 26,129 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 0.58 (26129 hom., cov: 32)
• Consequence: CLEC1B ENST00000398937.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532

Genes affected

CLEC1B (HGNC:24356): (C-type lectin domain family 1 member B) Natural killer (NK) cells express multiple calcium-dependent (C-type) lectin-like receptors, such as CD94 (KLRD1; MIM 602894) and NKG2D (KLRC4; MIM 602893), that interact with major histocompatibility complex class I molecules and either inhibit or activate cytotoxicity and cytokine secretion. CLEC2 is a C-type lectin-like receptor expressed in myeloid cells and NK cells (Colonna et al., 2000 [PubMed 10671229]).[supplied by OMIM, Jan 2011]

CLEC12A (HGNC:31713): (C-type lectin domain family 12 member A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signaling, glycoprotein turnover, and roles in inflammation and immune response. The protein encoded by this gene is a negative regulator of granulocyte and monocyte function. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. This gene is closely linked to other CTL/CTLD superfamily members in the natural killer gene complex region on chromosome 12p13. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC12A	XM_006719035.4	c.642-4720G>A		intron_variant			XP_006719098.2
CLEC12A	XM_011520573.3	c.642-4723G>A		intron_variant			XP_011518875.2
CLEC12A	XM_047428399.1	c.672-4720G>A		intron_variant			XP_047284355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC1B	ENST00000398937.6	c.267-4140C>T		intron_variant		3		ENSP00000381910
CLEC12A	ENST00000449959.6	n.1005-4720G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88203 AN: 151934 Hom.: 26104 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.581 AC: 88277 AN: 152052 Hom.: 26129 Cov.: 32 AF XY: 0.585 AC XY: 43510 AN XY: 74344

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.795

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.575

Alfa AF: 0.556 Hom.: 4004

Bravo AF: 0.579

Asia WGS AF: 0.791 AC: 2748 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs679982; hg19: chr12-10142897;