NM_021155.4:c.-201C>A

Variant names:

• chr19-7747712-G-T
• rs11465366
• NM_021155.4:c.-201C>A

Variant summary

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

The NM_021155.4(CD209):​c.-201C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00631 in 858,550 control chromosomes in the GnomAD database, including 237 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 0.024 (155 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (82 hom.)
• Consequence: CD209 NM_021155.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0807 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD209	NM_021155.4	MANE Select	c.-201C>A		upstream_gene	N/A	NP_066978.1
	CD209	NM_001144897.2		c.-201C>A		upstream_gene	N/A	NP_001138369.1
	CD209	NM_001144896.2		c.-201C>A		upstream_gene	N/A	NP_001138368.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD209	ENST00000315599.12	TSL:1 MANE Select	c.-201C>A		upstream_gene	N/A	ENSP00000315477.6
	CD209	ENST00000354397.10	TSL:1	c.-201C>A		upstream_gene	N/A	ENSP00000346373.5
	CD209	ENST00000315591.12	TSL:1	c.-201C>A		upstream_gene	N/A	ENSP00000315407.7

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3620 AN: 152180 Hom.: 154 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.00254 AC: 1793 AN: 706252 Hom.: 82 AF XY: 0.00217 AC XY: 777 AN XY: 358738

African (AFR) AF: 0.0812 AC: 1370 AN: 16880

American (AMR) AF: 0.00587 AC: 114 AN: 19418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15328

East Asian (EAS) AF: 0.00 AC: 0 AN: 32348

South Asian (SAS) AF: 0.000237 AC: 12 AN: 50674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32370

Middle Eastern (MID) AF: 0.000811 AC: 2 AN: 2466

European-Non Finnish (NFE) AF: 0.000161 AC: 81 AN: 502278

Other (OTH) AF: 0.00620 AC: 214 AN: 34490

GnomAD4 genome AF: 0.0238 AC: 3622 AN: 152298 Hom.: 155 Cov.: 32 AF XY: 0.0233 AC XY: 1732 AN XY: 74490

African (AFR) AF: 0.0830 AC: 3447 AN: 41538

American (AMR) AF: 0.00726 AC: 111 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68026

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.0500 Hom.: 89

Bravo AF: 0.0270

Asia WGS AF: 0.00462 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.39
PhyloP100		-2.4
PromoterAI		-0.24	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11465366; hg19: chr19-7812598;