rs10410342

Positions:

• chr19-7743566-G-C
• chr19-7743566-G-T

Variant summary

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

The NM_021155.4(CD209):​c.1014-326C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,140 control chromosomes in the GnomAD database, including 1,352 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 0.11 (1352 hom., cov: 32)
• Consequence: CD209 NM_021155.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

Genes affected

CD209 (HGNC:1641): (CD209 molecule) This gene encodes a C-type lectin that functions in cell adhesion and pathogen recognition. This receptor recognizes a wide range of evolutionarily divergent pathogens with a large impact on public health, including leprosy and tuberculosis mycobacteria, the Ebola, hepatitis C, HIV-1 and Dengue viruses, and the SARS-CoV acute respiratory syndrome coronavirus. The protein is organized into four distinct domains: a C-terminal carbohydrate recognition domain, a flexible tandem-repeat neck domain, a transmembrane region and an N-terminal cytoplasmic domain involved in internalization. This gene is closely related in terms of both sequence and function to a neighboring gene, CLEC4M (Gene ID: 10332), also known as L-SIGN. The two genes differ in viral recognition and expression patterns, with this gene showing high expression on the surface of dendritic cells. Polymorphisms in the neck region are associated with protection from HIV-1 infection, while single nucleotide polymorphisms in the promoter of this gene are associated with differing resistance and susceptibility to and severity of infectious disease, including rs4804803, which is associated with SARS severity. [provided by RefSeq, May 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD209	NM_021155.4	c.1014-326C>G		intron_variant		ENST00000315599.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD209	ENST00000315599.12	c.1014-326C>G		intron_variant		1	NM_021155.4	P2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16206 AN: 152022 Hom.: 1354 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0714

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.0654

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0510

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.107 AC: 16213 AN: 152140 Hom.: 1352 Cov.: 32 AF XY: 0.105 AC XY: 7821 AN XY: 74366

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.0712

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.0654

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0510

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.0267 Hom.: 18

Bravo AF: 0.116

Asia WGS AF: 0.0810 AC: 284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.28

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: rs10410342; hg19: chr19-7808452;