rs2287886

Variant names:

• chr19-7747650-A-G
• rs2287886
• NM_021155.4:c.-139T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-7747650-A-G
• chr19-7747650-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• Publications: 78 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021155.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD209	NM_021155.4	MANE Select	c.-139T>C		upstream_gene	N/A	NP_066978.1	Q9NNX6-1
	CD209	NM_001144897.2		c.-139T>C		upstream_gene	N/A	NP_001138369.1	Q9NNX6-2
	CD209	NM_001144896.2		c.-139T>C		upstream_gene	N/A	NP_001138368.1	Q9NNX6-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD209	ENST00000315599.12	TSL:1 MANE Select	c.-139T>C		upstream_gene	N/A	ENSP00000315477.6	Q9NNX6-1
	CD209	ENST00000354397.10	TSL:1	c.-139T>C		upstream_gene	N/A	ENSP00000346373.5	Q9NNX6-2
	CD209	ENST00000315591.12	TSL:1	c.-139T>C		upstream_gene	N/A	ENSP00000315407.7	Q9NNX6-6

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99551 AN: 151990 Hom.: 33192 Cov.: 32

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

African (AFR) AF: 0.750 AC: 21277 AN: 28366

American (AMR) AF: 0.667 AC: 19221 AN: 28816

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 12602 AN: 19880

East Asian (EAS) AF: 0.293 AC: 11097 AN: 37816

South Asian (SAS) AF: 0.548 AC: 37738 AN: 68818

European-Finnish (FIN) AF: 0.603 AC: 28419 AN: 47158

Middle Eastern (MID) AF: 0.635 AC: 2279 AN: 3590

European-Non Finnish (NFE) AF: 0.647 AC: 635763 AN: 982790

Other (OTH) AF: 0.633 AC: 33574 AN: 53034

GnomAD4 genome AF: 0.655 AC: 99651 AN: 152108 Hom.: 33236 Cov.: 32 AF XY: 0.649 AC XY: 48245 AN XY: 74344

African (AFR) AF: 0.742 AC: 30775 AN: 41490

American (AMR) AF: 0.668 AC: 10216 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2211 AN: 3468

East Asian (EAS) AF: 0.306 AC: 1587 AN: 5178

South Asian (SAS) AF: 0.531 AC: 2557 AN: 4816

European-Finnish (FIN) AF: 0.604 AC: 6388 AN: 10574

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43709 AN: 67970

Other (OTH) AF: 0.650 AC: 1374 AN: 2114

Alfa AF: 0.651 Hom.: 71369

Bravo AF: 0.665

Asia WGS AF: 0.493 AC: 1716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.6
DANN	Benign	0.48
PhyloP100		0.14
PromoterAI		0.12	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2287886; hg19: chr19-7812536; COSMIC: COSV52654702;