chr19-7747712-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021155.4(CD209):​c.-201C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000566 in 706,264 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: CD209 NM_021155.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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>T		upstream_gene	N/A	NP_066978.1
	CD209	NM_001144897.2		c.-201C>T		upstream_gene	N/A	NP_001138369.1
	CD209	NM_001144896.2		c.-201C>T		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>T		upstream_gene	N/A	ENSP00000315477.6
	CD209	ENST00000354397.10	TSL:1	c.-201C>T		upstream_gene	N/A	ENSP00000346373.5
	CD209	ENST00000315591.12	TSL:1	c.-201C>T		upstream_gene	N/A	ENSP00000315407.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000566 AC: 4 AN: 706264 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 358740

African (AFR) AF: 0.00 AC: 0 AN: 16886

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 50674

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2466

European-Non Finnish (NFE) AF: 0.00000796 AC: 4 AN: 502282

Other (OTH) AF: 0.00 AC: 0 AN: 34492

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.35
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;