19-7742141-A-G

Position:

• chr19-7742141-A-G

Variant summary

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

The ENST00000315599.12(CD209):​c.*898T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 215,238 control chromosomes in the GnomAD database, including 74,728 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 0.81 (51198 hom., cov: 30)
  • Exomes 𝑓: 0.86 (23530 hom.)
• Consequence: CD209 ENST00000315599.12 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.922

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=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD209	NM_021155.4	c.*898T>C		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.*898T>C		3_prime_UTR_variant	7/7	1	NM_021155.4	ENSP00000315477	P2

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123551 AN: 151932 Hom.: 51161 Cov.: 30

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.842

GnomAD4 exome AF: 0.861 AC: 54395 AN: 63188 Hom.: 23530 Cov.: 0 AF XY: 0.863 AC XY: 29934 AN XY: 34700

Gnomad4 AFR exome AF: 0.642

Gnomad4 AMR exome AF: 0.869

Gnomad4 ASJ exome AF: 0.886

Gnomad4 EAS exome AF: 0.727

Gnomad4 SAS exome AF: 0.815

Gnomad4 FIN exome AF: 0.865

Gnomad4 NFE exome AF: 0.890

Gnomad4 OTH exome AF: 0.871

GnomAD4 genome AF: 0.813 AC: 123638 AN: 152050 Hom.: 51198 Cov.: 30 AF XY: 0.812 AC XY: 60386 AN XY: 74334

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.897

Gnomad4 OTH AF: 0.843

Alfa AF: 0.879 Hom.: 77623

Bravo AF: 0.808

Asia WGS AF: 0.777 AC: 2701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.3
DANN	Benign	0.60

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: rs7248637; hg19: chr19-7807027;