12-9995604-T-C

Position:

• chr12-9995604-T-C

Variant summary

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

The NM_016509.4(CLEC1B):​c.439-358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0817 in 340,076 control chromosomes in the GnomAD database, including 1,273 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 0.074 (455 hom., cov: 32)
  • Exomes 𝑓: 0.088 (818 hom.)
• Consequence: CLEC1B NM_016509.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC1B	NM_016509.4	c.439-358A>G		intron_variant		ENST00000298527.11	NP_057593.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC1B	ENST00000298527.11	c.439-358A>G		intron_variant		1	NM_016509.4	ENSP00000298527	P1

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11195 AN: 152070 Hom.: 456 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0536

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0863

Gnomad OTH AF: 0.0761

GnomAD4 exome AF: 0.0883 AC: 16582 AN: 187888 Hom.: 818 Cov.: 0 AF XY: 0.0896 AC XY: 9315 AN XY: 103944

Gnomad4 AFR exome AF: 0.0507

Gnomad4 AMR exome AF: 0.0434

Gnomad4 ASJ exome AF: 0.0622

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.0576

Gnomad4 NFE exome AF: 0.0857

Gnomad4 OTH exome AF: 0.0859

GnomAD4 genome AF: 0.0735 AC: 11193 AN: 152188 Hom.: 455 Cov.: 32 AF XY: 0.0728 AC XY: 5420 AN XY: 74408

Gnomad4 AFR AF: 0.0496

Gnomad4 AMR AF: 0.0535

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0536

Gnomad4 NFE AF: 0.0863

Gnomad4 OTH AF: 0.0763

Alfa AF: 0.0821 Hom.: 710

Bravo AF: 0.0720

Asia WGS AF: 0.106 AC: 365 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.0
DANN	Benign	0.74

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: rs3818343; hg19: chr12-10148203;