19-7745673-C-T

Position:

• chr19-7745673-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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]

ENSG00000288669 (HGNC:):

ACMG classification

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 GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD209	NM_021155.4	c.593G>A	p.Arg198Gln	missense_variant	4/7	ENST00000315599.12	NP_066978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD209	ENST00000315599.12	c.593G>A	p.Arg198Gln	missense_variant	4/7	1	NM_021155.4	ENSP00000315477.6
ENSG00000288669	ENST00000678003.1	n.-11G>A		upstream_gene_variant				ENSP00000504497.1

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 341 AN: 136178 Hom.: 2 Cov.: 27

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000494

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000232

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000307

Gnomad OTH AF: 0.00266

GnomAD3 exomes AF: 0.0000513 AC: 12 AN: 234060 Hom.: 1 AF XY: 0.0000623 AC XY: 8 AN XY: 128380

Gnomad AFR exome AF: 0.000921

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000147 AC: 7 AN: 475178 Hom.: 0 Cov.: 0 AF XY: 0.0000195 AC XY: 5 AN XY: 256084

Gnomad4 AFR exome AF: 0.000191

Gnomad4 AMR exome AF: 0.0000519

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000689

Gnomad4 OTH exome AF: 0.0000744

GnomAD4 genome AF: 0.00251 AC: 342 AN: 136262 Hom.: 2 Cov.: 27 AF XY: 0.00262 AC XY: 174 AN XY: 66480

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.000494

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000233

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000307

Gnomad4 OTH AF: 0.00263

Alfa AF: 0.000516 Hom.: 0

ExAC AF: 0.00000844 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.011
DANN	Benign	0.26
DEOGEN2	Benign	0.051	T;T;.;.;.;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00035	N
LIST_S2	Benign	0.46	T;T;T;T;T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.014	T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.3	N;.;.;N;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.81	N;.;.;N;N;N;.
REVEL	Benign	0.026
Sift	Benign	1.0	T;.;.;T;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.012	B;.;B;B;B;B;B
Vest4		0.13
MVP		0.072
MPC		0.062
ClinPred		0.0086	T
GERP RS		-2.1
Varity_R		0.015
gMVP		0.033

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: rs41374747; hg19: chr19-7810559; COSMIC: COSV52656716;