rs10505747

Variant names:

• chr12-10046658-A-G
• rs10505747
• NM_207345.4:c.-163+5038A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207345.4(CLEC9A):​c.-163+5038A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 152,270 control chromosomes in the GnomAD database, including 426 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 0.048 (426 hom., cov: 32)
• Consequence: CLEC9A NM_207345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 0 publications found

Genes affected

CLEC9A (HGNC:26705): (C-type lectin domain containing 9A) CLEC9A is a group V C-type lectin-like receptor (CTLR) that functions as an activation receptor and is expressed on myeloid lineage cells (Huysamen et al., 2008 [PubMed 18408006]).[supplied by OMIM, Aug 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC9A	NM_207345.4	c.-163+5038A>G		intron_variant	Intron 2 of 8	ENST00000355819.6	NP_997228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC9A	ENST00000355819.6	c.-163+5038A>G		intron_variant	Intron 2 of 8	1	NM_207345.4	ENSP00000348074.1
CLEC9A	ENST00000544751.1	n.450+5038A>G		intron_variant	Intron 2 of 2	1

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7254 AN: 152152 Hom.: 425 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.0962

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00298

Gnomad OTH AF: 0.0387

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

GnomAD4 genome AF: 0.0478 AC: 7273 AN: 152270 Hom.: 426 Cov.: 32 AF XY: 0.0488 AC XY: 3634 AN XY: 74472

African (AFR) AF: 0.139 AC: 5776 AN: 41544

American (AMR) AF: 0.0169 AC: 258 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3470

East Asian (EAS) AF: 0.0961 AC: 498 AN: 5184

South Asian (SAS) AF: 0.0412 AC: 199 AN: 4826

European-Finnish (FIN) AF: 0.0187 AC: 198 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00298 AC: 203 AN: 68016

Other (OTH) AF: 0.0388 AC: 82 AN: 2116

Alfa AF: 0.0209 Hom.: 425

Bravo AF: 0.0517

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.74
PhyloP100		-0.093
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: rs10505747; hg19: chr12-10199257;