12-9995604-T-C

Variant names:

• chr12-9995604-T-C
• rs3818343
• NM_016509.4:c.439-358A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CLEC1B	NM_016509.4	c.439-358A>G		intron_variant	Intron 4 of 5	ENST00000298527.11	NP_057593.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC1B	ENST00000298527.11	c.439-358A>G		intron_variant	Intron 4 of 5	1	NM_016509.4	ENSP00000298527.6

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

African (AFR) AF: 0.0507 AC: 243 AN: 4792

American (AMR) AF: 0.0434 AC: 345 AN: 7952

Ashkenazi Jewish (ASJ) AF: 0.0622 AC: 270 AN: 4338

East Asian (EAS) AF: 0.148 AC: 1093 AN: 7390

South Asian (SAS) AF: 0.109 AC: 4072 AN: 37398

European-Finnish (FIN) AF: 0.0576 AC: 486 AN: 8444

Middle Eastern (MID) AF: 0.0734 AC: 48 AN: 654

European-Non Finnish (NFE) AF: 0.0857 AC: 9250 AN: 107896

Other (OTH) AF: 0.0859 AC: 775 AN: 9024

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

African (AFR) AF: 0.0496 AC: 2061 AN: 41548

American (AMR) AF: 0.0535 AC: 818 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3468

East Asian (EAS) AF: 0.162 AC: 839 AN: 5178

South Asian (SAS) AF: 0.112 AC: 538 AN: 4824

European-Finnish (FIN) AF: 0.0536 AC: 568 AN: 10588

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0863 AC: 5867 AN: 67982

Other (OTH) AF: 0.0763 AC: 161 AN: 2110

Alfa AF: 0.0810 Hom.: 840

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
PhyloP100		2.5
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: rs3818343; hg19: chr12-10148203;