chr19-7745120-G-A

Variant names:

• chr19-7745120-G-A
• rs11465384
• NM_021155.4:c.749-28C>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.749-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 1,612,932 control chromosomes in the GnomAD database, including 5,507 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 0.063 (425 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5082 hom.)
• Consequence: CD209 NM_021155.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD209	NM_021155.4	c.749-28C>T		intron_variant	Intron 4 of 6	ENST00000315599.12	NP_066978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD209	ENST00000315599.12	c.749-28C>T		intron_variant	Intron 4 of 6	1	NM_021155.4	ENSP00000315477.6
ENSG00000288669	ENST00000678003.1	n.145+398C>T		intron_variant	Intron 1 of 12			ENSP00000504497.1

Frequencies

GnomAD3 genomes AF: 0.0628 AC: 9555 AN: 152094 Hom.: 426 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.0555

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0584

GnomAD2 exomes AF: 0.0653 AC: 16343 AN: 250458 AF XY: 0.0655

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.0446

Gnomad ASJ exome AF: 0.0859

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.0876

Gnomad OTH exome AF: 0.0836

GnomAD4 exome AF: 0.0791 AC: 115597 AN: 1460720 Hom.: 5082 Cov.: 32 AF XY: 0.0781 AC XY: 56772 AN XY: 726682

African (AFR) AF: 0.0125 AC: 417 AN: 33470

American (AMR) AF: 0.0466 AC: 2083 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0866 AC: 2256 AN: 26058

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39692

South Asian (SAS) AF: 0.0268 AC: 2306 AN: 86182

European-Finnish (FIN) AF: 0.110 AC: 5886 AN: 53376

Middle Eastern (MID) AF: 0.0888 AC: 512 AN: 5766

European-Non Finnish (NFE) AF: 0.0880 AC: 97797 AN: 1111124

Other (OTH) AF: 0.0718 AC: 4334 AN: 60348

GnomAD4 genome AF: 0.0627 AC: 9547 AN: 152212 Hom.: 425 Cov.: 32 AF XY: 0.0634 AC XY: 4716 AN XY: 74388

African (AFR) AF: 0.0153 AC: 636 AN: 41550

American (AMR) AF: 0.0554 AC: 847 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0263 AC: 127 AN: 4824

European-Finnish (FIN) AF: 0.118 AC: 1245 AN: 10570

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0883 AC: 6005 AN: 68002

Other (OTH) AF: 0.0583 AC: 123 AN: 2110

Alfa AF: 0.0587 Hom.: 305

Bravo AF: 0.0572

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.64
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11465384; hg19: chr19-7810006;