Variant 19-7744193-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The ENST00000315599.12(CD209):c.927A>G(p.Arg309=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00956 in 1,614,038 control chromosomes in the GnomAD database, including 549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.036 ( 258 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 291 hom. )

Consequence

CD209
ENST00000315599.12 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.252

Variant links:

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]

CD209 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 19-7744193-T-C is Benign according to our data. Variant chr19-7744193-T-C is described in ClinVar as [Benign]. Clinvar id is 3039142.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.252 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD209	NM_021155.4 linkuse as main transcript	c.927A>G	p.Arg309=	synonymous_variant	6/7	ENST00000315599.12	NP_066978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD209	ENST00000315599.12 linkuse as main transcript	c.927A>G	p.Arg309=	synonymous_variant	6/7	1	NM_021155.4	ENSP00000315477	P2	Q9NNX6-1

Frequencies

GnomAD3 genomes

AF:

0.0360

AC:

5480

AN:

152174

Hom.:

258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.0505

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00426

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0120

AC:

3008

AN:

251484

Hom.:

130

AF XY:

0.00963

AC XY:

1309

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00150

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00483

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.00680

AC:

9944

AN:

1461746

Hom.:

291

Cov.:

AF XY:

0.00625

AC XY:

4547

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.0128

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00148

Gnomad4 FIN exome

AF:

0.000936

Gnomad4 NFE exome

AF:

0.00386

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.0360

AC:

5483

AN:

152292

Hom.:

258

Cov.:

AF XY:

0.0351

AC XY:

2613

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.0199

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00423

Gnomad4 OTH

AF:

0.0308

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0408

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CD209-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 29, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.2

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over