chr19-7740242-G-C

Variant names:

• chr19-7740242-G-C
• rs4804800
• NM_021155.4:c.*2797C>G

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.*2797C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 239,864 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: 31)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: CD209 NM_021155.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88

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: 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=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD209	NM_021155.4	c.*2797C>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000315599.12	NP_066978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD209	ENST00000315599.12	c.*2797C>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_021155.4	ENSP00000315477.6
ENSG00000288669	ENST00000678003.1	n.*290+1325C>G		intron_variant	Intron 2 of 12			ENSP00000504497.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000417 AC: 1 AN: 239864 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 129160

African (AFR) AF: 0.00 AC: 0 AN: 6646

American (AMR) AF: 0.00 AC: 0 AN: 8218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6630

East Asian (EAS) AF: 0.00 AC: 0 AN: 11844

South Asian (SAS) AF: 0.00 AC: 0 AN: 32632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1006

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 145462

Other (OTH) AF: 0.0000762 AC: 1 AN: 13128

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 67976

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.26
DANN	Benign	0.15
PhyloP100		-2.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

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Other links and lift over

dbSNP: rs4804800; hg19: chr19-7805128;