rs1544767

Positions:

• chr19-7741982-T-A
• chr19-7741982-T-C

Variant summary

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

The ENST00000315599.12(CD209):​c.*1057A>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 348,674 control chromosomes in the GnomAD database, including 159,749 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 0.94 (67170 hom., cov: 28)
  • Exomes 𝑓: 0.97 (92579 hom.)
• Consequence: CD209 ENST00000315599.12 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.94).
• 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.*1057A>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.*1057A>T		3_prime_UTR_variant	7/7	1	NM_021155.4	ENSP00000315477	P2

Frequencies

GnomAD3 genomes AF: 0.937 AC: 142201 AN: 151736 Hom.: 67129 Cov.: 28

Gnomad AFR AF: 0.841

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.893

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.952

GnomAD4 exome AF: 0.968 AC: 190432 AN: 196820 Hom.: 92579 Cov.: 0 AF XY: 0.964 AC XY: 105640 AN XY: 109630

Gnomad4 AFR exome AF: 0.845

Gnomad4 AMR exome AF: 0.937

Gnomad4 ASJ exome AF: 0.997

Gnomad4 EAS exome AF: 0.716

Gnomad4 SAS exome AF: 0.919

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.974

GnomAD4 genome AF: 0.937 AC: 142300 AN: 151854 Hom.: 67170 Cov.: 28 AF XY: 0.935 AC XY: 69330 AN XY: 74162

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.950

Gnomad4 ASJ AF: 0.995

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.894

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.952

Alfa AF: 0.979 Hom.: 40548

Bravo AF: 0.929

Asia WGS AF: 0.822 AC: 2861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.65
DANN	Benign	0.72

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: rs1544767; hg19: chr19-7806868;