chr19-7745673-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_021155.4(CD209):c.593G>A(p.Arg198Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 136,262 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0025 ( 2 hom., cov: 27)
Exomes 𝑓: 0.000015 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CD209
NM_021155.4 missense
NM_021155.4 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: -0.341
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.013873458).
BP6
?
Variant 19-7745673-C-T is Benign according to our data. Variant chr19-7745673-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649176.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CD209 | NM_021155.4 | c.593G>A | p.Arg198Gln | missense_variant | 4/7 | ENST00000315599.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CD209 | ENST00000315599.12 | c.593G>A | p.Arg198Gln | missense_variant | 4/7 | 1 | NM_021155.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00250 AC: 341AN: 136178Hom.: 2 Cov.: 27
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GnomAD3 exomes AF: 0.0000513 AC: 12AN: 234060Hom.: 1 AF XY: 0.0000623 AC XY: 8AN XY: 128380
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000147 AC: 7AN: 475178Hom.: 0 Cov.: 0 AF XY: 0.0000195 AC XY: 5AN XY: 256084
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? AF: 0.00251 AC: 342AN: 136262Hom.: 2 Cov.: 27 AF XY: 0.00262 AC XY: 174AN XY: 66480
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | CD209: BP4, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;N;.;.;.
MutationTaster
Benign
N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;N;N;N;.
REVEL
Benign
Sift
Benign
T;.;.;T;T;T;.
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
B;.;B;B;B;B;B
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at