chr19-7744193-T-C

Position:

• chr19-7744193-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The ENST00000394161.9(CD209):​c.219A>G​(p.Arg73Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00956 in 1,614,038 control chromosomes in the GnomAD database, including 549 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.036 (258 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (291 hom.)
• Consequence: CD209 ENST00000394161.9 splice_region, synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.252

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-7744193-T-C is Benign according to our data. Variant chr19-7744193-T-C is described in ClinVar as [Benign]. Clinvar id is 3039142.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.252 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD209	NM_021155.4	c.927A>G	p.Arg309Arg	synonymous_variant	6/7	ENST00000315599.12	NP_066978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD209	ENST00000315599.12	c.927A>G	p.Arg309Arg	synonymous_variant	6/7	1	NM_021155.4	ENSP00000315477.6
ENSG00000288669	ENST00000678003.1	n.145+1325A>G		intron_variant				ENSP00000504497.1

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5480 AN: 152174 Hom.: 258 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00426

Gnomad OTH AF: 0.0306

GnomAD3 exomes AF: 0.0120 AC: 3008 AN: 251484 Hom.: 130 AF XY: 0.00963 AC XY: 1309 AN XY: 135914

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.0119

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00150

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.00483

Gnomad OTH exome AF: 0.00929

GnomAD4 exome AF: 0.00680 AC: 9944 AN: 1461746 Hom.: 291 Cov.: 31 AF XY: 0.00625 AC XY: 4547 AN XY: 727196

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.0128

Gnomad4 ASJ exome AF: 0.00184

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00148

Gnomad4 FIN exome AF: 0.000936

Gnomad4 NFE exome AF: 0.00386

Gnomad4 OTH exome AF: 0.0131

GnomAD4 genome AF: 0.0360 AC: 5483 AN: 152292 Hom.: 258 Cov.: 32 AF XY: 0.0351 AC XY: 2613 AN XY: 74466

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00423

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0187 Hom.: 47

Bravo AF: 0.0408

Asia WGS AF: 0.00635 AC: 23 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CD209-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 29, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17159887; hg19: chr19-7809079;