ENST00000398937.6:c.267-4140C>T

Variant names:

• chr12-9990298-G-A
• rs679982
• ENST00000398937.6:c.267-4140C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000398937.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC1B	ENST00000398937.6	TSL:3	c.267-4140C>T		intron	N/A	ENSP00000381910.2
	CLEC12A	ENST00000449959.6	TSL:2	n.1005-4720G>A		intron	N/A

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

African (AFR) AF: 0.585 AC: 24244 AN: 41474

American (AMR) AF: 0.584 AC: 8909 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1972 AN: 3470

East Asian (EAS) AF: 0.873 AC: 4522 AN: 5178

South Asian (SAS) AF: 0.795 AC: 3834 AN: 4822

European-Finnish (FIN) AF: 0.514 AC: 5433 AN: 10568

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37438 AN: 67968

Other (OTH) AF: 0.575 AC: 1216 AN: 2116

Alfa AF: 0.556 Hom.: 4125

Bravo AF: 0.579

Asia WGS AF: 0.791 AC: 2748 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.11
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs679982; hg19: chr12-10142897;