19-7742141-A-G

Variant names:

• chr19-7742141-A-G
• rs7248637
• NM_021155.4:c.*898T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021155.4(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 NM_021155.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.922
• Publications: 25 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=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.891 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.*898T>C		3_prime_UTR	Exon 7 of 7	NP_066978.1
	CD209	NM_001144897.2		c.*898T>C		3_prime_UTR	Exon 7 of 7	NP_001138369.1
	CD209	NM_001144896.2		c.*898T>C		3_prime_UTR	Exon 6 of 6	NP_001138368.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD209	ENST00000315599.12	TSL:1 MANE Select	c.*898T>C		3_prime_UTR	Exon 7 of 7	ENSP00000315477.6
	ENSG00000288669	ENST00000678003.1		n.146-244T>C		intron	N/A	ENSP00000504497.1
	ENSG00000288669	ENST00000678227.1		n.5T>C		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.642 AC: 915 AN: 1426

American (AMR) AF: 0.869 AC: 4887 AN: 5626

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 624 AN: 704

East Asian (EAS) AF: 0.727 AC: 2359 AN: 3246

South Asian (SAS) AF: 0.815 AC: 4027 AN: 4942

European-Finnish (FIN) AF: 0.865 AC: 14604 AN: 16886

Middle Eastern (MID) AF: 0.878 AC: 79 AN: 90

European-Non Finnish (NFE) AF: 0.890 AC: 24900 AN: 27972

Other (OTH) AF: 0.871 AC: 2000 AN: 2296

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

African (AFR) AF: 0.646 AC: 26751 AN: 41418

American (AMR) AF: 0.874 AC: 13359 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3068 AN: 3472

East Asian (EAS) AF: 0.718 AC: 3702 AN: 5156

South Asian (SAS) AF: 0.814 AC: 3917 AN: 4814

European-Finnish (FIN) AF: 0.863 AC: 9126 AN: 10572

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.897 AC: 60982 AN: 68020

Other (OTH) AF: 0.843 AC: 1777 AN: 2108

Alfa AF: 0.857 Hom.: 106647

Bravo AF: 0.808

Asia WGS AF: 0.777 AC: 2701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.3
DANN	Benign	0.60
PhyloP100		0.92
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: rs7248637; hg19: chr19-7807027;