Variant 19-7744127-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000315599.12(CD209):c.993C>T(p.Asp331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00807 in 1,613,644 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 76 hom. )

Consequence

CD209
ENST00000315599.12 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.27

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-7744127-G-A is Benign according to our data. Variant chr19-7744127-G-A is described in ClinVar as [Benign]. Clinvar id is 777898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.27 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD209	NM_021155.4 linkuse as main transcript	c.993C>T	p.Asp331=	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 linkuse as main transcript	c.993C>T	p.Asp331=	synonymous_variant	6/7	1	NM_021155.4	ENSP00000315477	P2	Q9NNX6-1

Frequencies

GnomAD3 genomes

AF:

0.00769

AC:

1171

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.0395

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00961

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00876

AC:

2204

AN:

251478

Hom.:

AF XY:

0.00912

AC XY:

1239

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.0340

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00679

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00812

AC:

11859

AN:

1461338

Hom.:

Cov.:

AF XY:

0.00822

AC XY:

5975

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00463

Gnomad4 ASJ exome

AF:

0.0329

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00609

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.00815

Gnomad4 OTH exome

AF:

0.00868

GnomAD4 genome

AF:

0.00769

AC:

1171

AN:

152306

Hom.:

Cov.:

AF XY:

0.00783

AC XY:

583

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.0395

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.00961

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.00731

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0105

EpiControl

AF:

0.0122

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	CD209: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.84

DANN

Benign

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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