rs10505742

Variant names:

• chr12-9999979-T-A
• rs10505742
• ENST00000428126.6:c.-200-679A>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001393342.1(CLEC1B):​c.-200-679A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,322 control chromosomes in the GnomAD database, including 56 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 0.023 (56 hom., cov: 33)
• Consequence: CLEC1B NM_001393342.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207

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=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0229 (3483/152322) while in subpopulation NFE AF= 0.0356 (2421/68008). AF 95% confidence interval is 0.0344. There are 56 homozygotes in gnomad4. There are 1624 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC1B	NM_001393342.1	c.-200-679A>T		intron_variant	Intron 2 of 7		NP_001380271.1
CLEC1B	XM_047428938.1	c.-200-679A>T		intron_variant	Intron 2 of 7		XP_047284894.1
CLEC12A	XM_047428402.1	c.642-6114T>A		intron_variant	Intron 5 of 5		XP_047284358.1
CLEC1B	XM_011520685.3	c.-200-679A>T		intron_variant	Intron 2 of 6		XP_011518987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC1B	ENST00000428126.6	c.-200-679A>T		intron_variant	Intron 2 of 6	1		ENSP00000406338.2

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3480 AN: 152204 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.00617

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0356

Gnomad OTH AF: 0.0258

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

GnomAD4 genome AF: 0.0229 AC: 3483 AN: 152322 Hom.: 56 Cov.: 33 AF XY: 0.0218 AC XY: 1624 AN XY: 74488

Gnomad4 AFR AF: 0.00616

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.0427

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0161

Gnomad4 FIN AF: 0.0222

Gnomad4 NFE AF: 0.0356

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0307 Hom.: 16

Bravo AF: 0.0214

Asia WGS AF: 0.00954 AC: 33 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10505742; hg19: chr12-10152578;