19-7744127-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_021155.4(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 NM_021155.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.27

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]

ACMG classification

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 GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD209	NM_021155.4	c.993C>T	p.Asp331=	synonymous_variant	6/7	ENST00000315599.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD209	ENST00000315599.12	c.993C>T	p.Asp331=	synonymous_variant	6/7	1	NM_021155.4	P2

Frequencies

GnomAD3 genomes AF: 0.00769 AC: 1171 AN: 152188 Hom.: 10 Cov.: 32

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.: 21 AF XY: 0.00912 AC XY: 1239 AN XY: 135910

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.: 76 Cov.: 31 AF XY: 0.00822 AC XY: 5975 AN XY: 727020

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.: 10 Cov.: 32 AF XY: 0.00783 AC XY: 583 AN XY: 74466

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.: 7

Bravo AF: 0.00731

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0105

EpiControl AF: 0.0122

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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	clinical testing	Invitae	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

Other links and lift over

dbSNP: rs78866372; hg19: chr19-7809013; COSMIC: COSV52656555;