chr19-7742596-T-A

Variant names:

• chr19-7742596-T-A
• rs4804801
• NM_021155.4:c.*443A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021155.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD209	NM_021155.4	MANE Select	c.*443A>T		3_prime_UTR	Exon 7 of 7	NP_066978.1	Q9NNX6-1
	CD209	NM_001144897.2		c.*443A>T		3_prime_UTR	Exon 7 of 7	NP_001138369.1	Q9NNX6-2
	CD209	NM_001144896.2		c.*443A>T		3_prime_UTR	Exon 6 of 6	NP_001138368.1	Q9NNX6-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD209	ENST00000315599.12	TSL:1 MANE Select	c.*443A>T		3_prime_UTR	Exon 7 of 7	ENSP00000315477.6	Q9NNX6-1
	ENSG00000288669	ENST00000678003.1		n.146-699A>T		intron	N/A	ENSP00000504497.1	A0A7I2YQT4
	CD209	ENST00000394173.8	TSL:2	c.*443A>T		3_prime_UTR	Exon 7 of 7	ENSP00000377728.4	X6RB12

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

African (AFR) AF: 0.353 AC: 415 AN: 1176

American (AMR) AF: 0.896 AC: 2996 AN: 3342

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 487 AN: 534

East Asian (EAS) AF: 0.633 AC: 1313 AN: 2074

South Asian (SAS) AF: 0.825 AC: 2150 AN: 2606

European-Finnish (FIN) AF: 0.963 AC: 657 AN: 682

Middle Eastern (MID) AF: 0.932 AC: 69 AN: 74

European-Non Finnish (NFE) AF: 0.953 AC: 14246 AN: 14952

Other (OTH) AF: 0.906 AC: 1114 AN: 1230

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

African (AFR) AF: 0.417 AC: 17262 AN: 41358

American (AMR) AF: 0.862 AC: 13170 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3154 AN: 3472

East Asian (EAS) AF: 0.628 AC: 3248 AN: 5168

South Asian (SAS) AF: 0.783 AC: 3766 AN: 4810

European-Finnish (FIN) AF: 0.975 AC: 10342 AN: 10610

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64345 AN: 68004

Other (OTH) AF: 0.819 AC: 1730 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
DANN	Benign	0.33
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4804801; hg19: chr19-7807482;