rs11465384

Positions:

• chr19-7745120-G-A
• chr19-7745120-G-C

Variant summary

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

The NM_021155.4(CD209):​c.749-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 1,612,932 control chromosomes in the GnomAD database, including 5,507 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 0.063 (425 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5082 hom.)
• Consequence: CD209 NM_021155.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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]

ENSG00000288669 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.0864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD209	NM_021155.4	c.749-28C>T		intron_variant		ENST00000315599.12	NP_066978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD209	ENST00000315599.12	c.749-28C>T		intron_variant		1	NM_021155.4	ENSP00000315477.6
ENSG00000288669	ENST00000678003.1	n.145+398C>T		intron_variant				ENSP00000504497.1

Frequencies

GnomAD3 genomes AF: 0.0628 AC: 9555 AN: 152094 Hom.: 426 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.0555

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0584

GnomAD3 exomes AF: 0.0653 AC: 16343 AN: 250458 Hom.: 730 AF XY: 0.0655 AC XY: 8864 AN XY: 135350

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.0446

Gnomad ASJ exome AF: 0.0859

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0271

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.0876

Gnomad OTH exome AF: 0.0836

GnomAD4 exome AF: 0.0791 AC: 115597 AN: 1460720 Hom.: 5082 Cov.: 32 AF XY: 0.0781 AC XY: 56772 AN XY: 726682

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.0466

Gnomad4 ASJ exome AF: 0.0866

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0268

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0880

Gnomad4 OTH exome AF: 0.0718

GnomAD4 genome AF: 0.0627 AC: 9547 AN: 152212 Hom.: 425 Cov.: 32 AF XY: 0.0634 AC XY: 4716 AN XY: 74388

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.0554

Gnomad4 ASJ AF: 0.0922

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0263

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0883

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0520 Hom.: 66

Bravo AF: 0.0572

Asia WGS AF: 0.0140 AC: 51 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	2.8
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11465384; hg19: chr19-7810006;