19-7742596-T-A

Position:

• chr19-7742596-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021155.4(CD209):​c.*443A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 178,690 control chromosomes in the GnomAD database, including 60,598 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 0.78 (49977 hom., cov: 30)
  • Exomes 𝑓: 0.88 (10621 hom.)
• Consequence: CD209 NM_021155.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD209	NM_021155.4	c.*443A>T		3_prime_UTR_variant	7/7	ENST00000315599.12	NP_066978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD209	ENST00000315599.12	c.*443A>T		3_prime_UTR_variant	7/7	1	NM_021155.4	ENSP00000315477	P2
CD209	ENST00000394173.8	c.*443A>T		3_prime_UTR_variant	7/7	2		ENSP00000377728

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118029 AN: 151902 Hom.: 49962 Cov.: 30

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.818

GnomAD4 exome AF: 0.879 AC: 23447 AN: 26670 Hom.: 10621 Cov.: 0 AF XY: 0.879 AC XY: 12183 AN XY: 13866

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.896

Gnomad4 ASJ exome AF: 0.912

Gnomad4 EAS exome AF: 0.633

Gnomad4 SAS exome AF: 0.825

Gnomad4 FIN exome AF: 0.963

Gnomad4 NFE exome AF: 0.953

Gnomad4 OTH exome AF: 0.906

GnomAD4 genome AF: 0.777 AC: 118085 AN: 152020 Hom.: 49977 Cov.: 30 AF XY: 0.778 AC XY: 57828 AN XY: 74336

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.946

Gnomad4 OTH AF: 0.819

Alfa AF: 0.847 Hom.: 7128

Bravo AF: 0.753

Asia WGS AF: 0.700 AC: 2435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
DANN	Benign	0.33

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

LitVar

Other links and lift over

dbSNP: rs4804801; hg19: chr19-7807482;