NM_021155.4:c.927A>G

Variant names:

• chr19-7744193-T-C
• rs17159887
• NM_021155.4:c.927A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_021155.4(CD209):​c.927A>G​(p.Arg309Arg) 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 NM_021155.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.252
• Publications: 4 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]

ENSG00000288669 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.927A>G	p.Arg309Arg	synonymous	Exon 6 of 7	NP_066978.1	Q9NNX6-1
	CD209	NM_001144897.2		c.909A>G	p.Arg303Arg	synonymous	Exon 6 of 7	NP_001138369.1	Q9NNX6-2
	CD209	NM_001144896.2		c.855A>G	p.Arg285Arg	synonymous	Exon 5 of 6	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.927A>G	p.Arg309Arg	synonymous	Exon 6 of 7	ENSP00000315477.6	Q9NNX6-1
	CD209	ENST00000354397.10	TSL:1	c.909A>G	p.Arg303Arg	synonymous	Exon 6 of 7	ENSP00000346373.5	Q9NNX6-2
	CD209	ENST00000315591.12	TSL:1	c.855A>G	p.Arg285Arg	synonymous	Exon 5 of 6	ENSP00000315407.7	Q9NNX6-6

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5480 AN: 152174 Hom.: 258 Cov.: 32

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

GnomAD2 exomes AF: 0.0120 AC: 3008 AN: 251484 AF XY: 0.00963

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 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.: 31 AF XY: 0.00625 AC XY: 4547 AN XY: 727196

African (AFR) AF: 0.119 AC: 3995 AN: 33478

American (AMR) AF: 0.0128 AC: 574 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00184 AC: 48 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00148 AC: 128 AN: 86258

European-Finnish (FIN) AF: 0.000936 AC: 50 AN: 53410

Middle Eastern (MID) AF: 0.0114 AC: 66 AN: 5768

European-Non Finnish (NFE) AF: 0.00386 AC: 4290 AN: 1111894

Other (OTH) AF: 0.0131 AC: 793 AN: 60384

GnomAD4 genome AF: 0.0360 AC: 5483 AN: 152292 Hom.: 258 Cov.: 32 AF XY: 0.0351 AC XY: 2613 AN XY: 74466

African (AFR) AF: 0.114 AC: 4751 AN: 41550

American (AMR) AF: 0.0199 AC: 304 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4828

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10624

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00423 AC: 288 AN: 68034

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0195 Hom.: 54

Bravo AF: 0.0408

Asia WGS AF: 0.00635 AC: 23 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00593

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CD209-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.45
PhyloP100		0.25
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17159887; hg19: chr19-7809079;