rs11465413

chr19-7741065-A-T

Variant summary

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

The NM_021155.4(CD209):c.*1974T>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.13 in 820,240 control chromosomes in the GnomAD database, including 10,771 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 0.18 (4237 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6534 hom.)
• Consequence: CD209 NM_021155.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64

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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD209	NM_021155.4	c.*1974T>A		3_prime_UTR_variant	7/7	ENST00000315599.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD209	ENST00000315599.12	c.*1974T>A		3_prime_UTR_variant	7/7	1	NM_021155.4	P2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27296 AN: 152116 Hom.: 4206 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0844

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.118 AC: 78980 AN: 668004 Hom.: 6534 Cov.: 9 AF XY: 0.119 AC XY: 42718 AN XY: 358960

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.0685

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.0442

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.180 AC: 27375 AN: 152236 Hom.: 4237 Cov.: 32 AF XY: 0.177 AC XY: 13150 AN XY: 74436

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.0391

Gnomad4 NFE AF: 0.0844

Gnomad4 OTH AF: 0.150

Alfa AF: 0.131 Hom.: 316

Bravo AF: 0.192

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	2.2
Dann	Benign	0.64

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: rs11465413; hg19: chr19-7805951; COSMIC: COSV52654377; COSMIC: COSV52654377;