19-7745604-C-T

Position:

chr19-7745604-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_021155.4(CD209):c.662G>A(p.Arg221Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 617,018 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.013 ( 5 hom., cov: 30)

Exomes 𝑓: 0.00039 ( 2 hom. )

Consequence

CD209
NM_021155.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.640

Variant links:

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]

CD209 links:

ENSG00000288669 (HGNC:):

ENSG00000288669 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038184822).

BP6

Variant 19-7745604-C-T is Benign according to our data. Variant chr19-7745604-C-T is described in ClinVar as [Benign]. Clinvar id is 3038490.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1776/140266) while in subpopulation AFR AF= 0.0485 (1664/34320). AF 95% confidence interval is 0.0465. There are 5 homozygotes in gnomad4. There are 830 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD209	NM_021155.4 link	c.662G>A	p.Arg221Gln	missense_variant	4/7	ENST00000315599.12	NP_066978.1	Q9NNX6-1B2R907

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD209	ENST00000315599.12 link	c.662G>A	p.Arg221Gln	missense_variant	4/7	1	NM_021155.4	ENSP00000315477.6		Q9NNX6-1
ENSG00000288669	ENST00000678003.1 link	n.59G>A		non_coding_transcript_exon_variant	1/13			ENSP00000504497.1		A0A7I2YQT4

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1778

AN:

140142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00469

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000211

Gnomad SAS

AF:

0.000686

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00787

Gnomad NFE

AF:

0.000243

Gnomad OTH

AF:

0.0112

GnomAD3 exomes

AF:

0.000504

AC:

113

AN:

223996

Hom.:

AF XY:

0.000259

AC XY:

AN XY:

123446

show subpopulations

Gnomad AFR exome

AF:

0.00880

Gnomad AMR exome

AF:

0.0000656

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000118

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000754

Gnomad OTH exome

AF:

0.000553

GnomAD4 exome

AF:

0.000390

AC:

186

AN:

476752

Hom.:

Cov.:

AF XY:

0.000370

AC XY:

AN XY:

256682

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.000740

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000429

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.0127

AC:

1776

AN:

140266

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

830

AN XY:

68510

show subpopulations

Gnomad4 AFR

AF:

0.0485

Gnomad4 AMR

AF:

0.00468

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000212

Gnomad4 SAS

AF:

0.000686

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000243

Gnomad4 OTH

AF:

0.0111

Alfa

AF:

0.0170

Hom.:

ESP6500AA

AF:

0.0963

AC:

369

ESP6500EA

AF:

0.00738

AC:

ExAC

AF:

0.00253

AC:

300

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CD209-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 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

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.081

DANN

Benign

0.22

DEOGEN2

Benign

0.051

T;.;.;.;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.000050

LIST_S2

Benign

0.40

T;T;T;T;T;T

MetaRNN

Benign

0.0038

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.4

N;.;N;.;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

0.90

N;.;N;N;N;.

REVEL

Benign

0.020

Sift

Benign

1.0

T;.;T;T;T;.

Sift4G

Benign

0.96

T;T;T;T;T;T

Polyphen

0.0010

B;B;B;B;B;B

Vest4

0.075

MVP

0.072

MPC

0.062

ClinPred

0.0020

GERP RS

-1.1

Varity_R

0.015

gMVP

0.062

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over