dbSNP rs2287886: CD209:c.-139T>C (chr19-7747650-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021155.4(CD209):c.-139T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,422,376 control chromosomes in the GnomAD database, including 289,594 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 0.66 ( 33236 hom., cov: 32)

Exomes 𝑓: 0.63 ( 256358 hom. )

Consequence

CD209
NM_021155.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.136

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD209	NM_021155.4 link	c.-139T>C		upstream_gene_variant		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.-139T>C		upstream_gene_variant		1	NM_021155.4	ENSP00000315477.6		Q9NNX6-1

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99551

AN:

151990

Hom.:

33192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.741

Gnomad AMI

AF:

0.717

Gnomad AMR

AF:

0.668

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.604

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.643

Gnomad OTH

AF:

0.650

GnomAD4 exome

AF:

0.631

AC:

801970

AN:

1270268

Hom.:

256358

AF XY:

0.629

AC XY:

394582

AN XY:

627326

show subpopulations

Gnomad4 AFR exome

AF:

0.750

Gnomad4 AMR exome

AF:

0.667

Gnomad4 ASJ exome

AF:

0.634

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.548

Gnomad4 FIN exome

AF:

0.603

Gnomad4 NFE exome

AF:

0.647

Gnomad4 OTH exome

AF:

0.633

GnomAD4 genome

AF:

0.655

AC:

99651

AN:

152108

Hom.:

33236

Cov.:

AF XY:

0.649

AC XY:

48245

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.742

Gnomad4 AMR

AF:

0.668

Gnomad4 ASJ

AF:

0.638

Gnomad4 EAS

AF:

0.306

Gnomad4 SAS

AF:

0.531

Gnomad4 FIN

AF:

0.604

Gnomad4 NFE

AF:

0.643

Gnomad4 OTH

AF:

0.650

Alfa

AF:

0.645

Hom.:

45206

Bravo

AF:

0.665

Asia WGS

AF:

0.493

AC:

1716

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

3.6

DANN

Benign

0.48

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over