rs4804800

chr19-7740242-G-Achr19-7740242-G-Cchr19-7740242-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.*2797C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 391,618 control chromosomes in the GnomAD database, including 139,204 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 0.81 (50648 hom., cov: 31)
  • Exomes 𝑓: 0.86 (88556 hom.)
• Consequence: CD209 NM_021155.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD209	NM_021155.4	c.*2797C>T		3_prime_UTR_variant	7/7	ENST00000315599.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD209	ENST00000315599.12	c.*2797C>T		3_prime_UTR_variant	7/7	1	NM_021155.4	P2

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123262 AN: 151978 Hom.: 50606 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.826

GnomAD4 exome AF: 0.858 AC: 205534 AN: 239522 Hom.: 88556 Cov.: 0 AF XY: 0.857 AC XY: 110621 AN XY: 129008

Gnomad4 AFR exome AF: 0.678

Gnomad4 AMR exome AF: 0.860

Gnomad4 ASJ exome AF: 0.866

Gnomad4 EAS exome AF: 0.733

Gnomad4 SAS exome AF: 0.851

Gnomad4 FIN exome AF: 0.870

Gnomad4 NFE exome AF: 0.877

Gnomad4 OTH exome AF: 0.853

GnomAD4 genome AF: 0.811 AC: 123358 AN: 152096 Hom.: 50648 Cov.: 31 AF XY: 0.809 AC XY: 60199 AN XY: 74372

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.861

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.833

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.828

Alfa AF: 0.861 Hom.: 52023

Bravo AF: 0.803

Asia WGS AF: 0.778 AC: 2705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.41
Dann	Benign	0.61

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: rs4804800; hg19: chr19-7805128;