rs8105572

Positions:

• chr19-7744441-C-T

Variant summary

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

The NM_021155.4(CD209):​c.901-222G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,242 control chromosomes in the GnomAD database, including 1,955 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 0.15 (1955 hom., cov: 32)
• Consequence: CD209 NM_021155.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD209	NM_021155.4	c.901-222G>A		intron_variant		ENST00000315599.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD209	ENST00000315599.12	c.901-222G>A		intron_variant		1	NM_021155.4	P2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23284 AN: 152124 Hom.: 1955 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0646

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.137

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.153 AC: 23291 AN: 152242 Hom.: 1955 Cov.: 32 AF XY: 0.152 AC XY: 11335 AN XY: 74444

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0646

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.135

Alfa AF: 0.135 Hom.: 1547

Bravo AF: 0.154

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.44

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: rs8105572; hg19: chr19-7809327;