rs1544766

Positions:

• chr19-7741837-G-A

Variant summary

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

The NM_021155.4(CD209):​c.*1202C>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 0.954 in 483,978 control chromosomes in the GnomAD database, including 221,705 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 0.93 (66821 hom., cov: 30)
  • Exomes 𝑓: 0.96 (154884 hom.)
• Consequence: CD209 NM_021155.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD209	NM_021155.4	c.*1202C>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	c.*1202C>T		3_prime_UTR_variant	7/7	1	NM_021155.4	ENSP00000315477.6
ENSG00000288669	ENST00000678003.1	n.*20C>T		non_coding_transcript_exon_variant	2/13			ENSP00000504497.1
ENSG00000288669	ENST00000678003.1	n.*20C>T		3_prime_UTR_variant	2/13			ENSP00000504497.1

Frequencies

GnomAD3 genomes AF: 0.934 AC: 141850 AN: 151886 Hom.: 66784 Cov.: 30

Gnomad AFR AF: 0.831

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.894

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.948

GnomAD4 exome AF: 0.963 AC: 319813 AN: 331974 Hom.: 154884 Cov.: 3 AF XY: 0.961 AC XY: 178118 AN XY: 185266

Gnomad4 AFR exome AF: 0.830

Gnomad4 AMR exome AF: 0.934

Gnomad4 ASJ exome AF: 0.996

Gnomad4 EAS exome AF: 0.729

Gnomad4 SAS exome AF: 0.916

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.966

GnomAD4 genome AF: 0.934 AC: 141942 AN: 152004 Hom.: 66821 Cov.: 30 AF XY: 0.932 AC XY: 69210 AN XY: 74276

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.995

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.894

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.946

Alfa AF: 0.947 Hom.: 9862

Bravo AF: 0.926

Asia WGS AF: 0.818 AC: 2845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.89
DANN	Benign	0.85

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: rs1544766; hg19: chr19-7806723; COSMIC: COSV52660410; COSMIC: COSV52660410;