19-7745542-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_021155.4(CD209):c.724C>G(p.Leu242Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,608,966 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.010 ( 32 hom., cov: 31)

Exomes 𝑓: 0.00050 ( 10 hom. )

Consequence

CD209
NM_021155.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Publications

13 publications found

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:

ENSG00000288669 (HGNC:):

ENSG00000288669 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003434211).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0103 (1565/151830) while in subpopulation AFR AF = 0.0353 (1452/41156). AF 95% confidence interval is 0.0338. There are 32 homozygotes in GnomAd4. There are 774 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD209	NM_021155.4 link	c.724C>G	p.Leu242Val	missense_variant	Exon 4 of 7	ENST00000315599.12	NP_066978.1	Q9NNX6-1B2R907

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD209	ENST00000315599.12 link	c.724C>G	p.Leu242Val	missense_variant	Exon 4 of 7	1	NM_021155.4	ENSP00000315477.6		Q9NNX6-1
ENSG00000288669	ENST00000678003.1 link	n.121C>G		non_coding_transcript_exon_variant	Exon 1 of 13			ENSP00000504497.1		A0A7I2YQT4

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1562

AN:

151720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0353

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00767

GnomAD2 exomes

AF:

0.000989

AC:

247

AN:

249800

AF XY:

0.000747

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.000987

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.000496

AC:

723

AN:

1457136

Hom.:

Cov.:

AF XY:

0.000450

AC XY:

326

AN XY:

725068

show subpopulations

African (AFR)

AF:

0.0128

AC:

405

AN:

31520

American (AMR)

AF:

0.00133

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.000104

AC:

AN:

86142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53038

Middle Eastern (MID)

AF:

0.00402

AC:

AN:

4478

European-Non Finnish (NFE)

AF:

0.000104

AC:

116

AN:

1111564

Other (OTH)

AF:

0.00192

AC:

115

AN:

60048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

116

173

231

289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0103

AC:

1565

AN:

151830

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

774

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.0353

AC:

1452

AN:

41156

American (AMR)

AF:

0.00438

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

68008

Other (OTH)

AF:

0.00759

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

144

216

288

360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000381

Hom.:

Bravo

AF:

0.0124

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0393

AC:

173

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00386

AC:

467

EpiCase

AF:

0.000872

EpiControl

AF:

0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.4

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.19

T;.;.;.;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.69

T;T;T;T;T;T

MetaRNN

Benign

0.0034

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.;L;.;.;.

PhyloP100

1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.3

N;.;N;N;N;.

REVEL

Benign

0.026

Sift

Benign

0.050

D;.;D;T;D;.

Sift4G

Benign

0.061

T;T;D;T;T;T

Polyphen

0.0020

B;P;B;B;B;B

Vest4

0.20

MVP

0.16

MPC

0.090

ClinPred

0.0044

GERP RS

0.74

Varity_R

0.055

gMVP

0.15

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over