19-7745542-G-C

Position:

• chr19-7745542-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_021155.4(CD209):​c.724C>G​(p.Leu242Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,608,966 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.010 (32 hom., cov: 31)
  • Exomes 𝑓: 0.00050 (10 hom.)
• Consequence: CD209 NM_021155.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003434211).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1565/151830) while in subpopulation AFR AF= 0.0353 (1452/41156). AF 95% confidence interval is 0.0338. There are 32 homozygotes in gnomad4. There are 774 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD209	NM_021155.4	c.724C>G	p.Leu242Val	missense_variant	4/7	ENST00000315599.12	NP_066978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD209	ENST00000315599.12	c.724C>G	p.Leu242Val	missense_variant	4/7	1	NM_021155.4	ENSP00000315477.6
ENSG00000288669	ENST00000678003.1	n.121C>G		non_coding_transcript_exon_variant	1/13			ENSP00000504497.1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1562 AN: 151720 Hom.: 32 Cov.: 31

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00767

GnomAD3 exomes AF: 0.000989 AC: 247 AN: 249800 Hom.: 5 AF XY: 0.000747 AC XY: 101 AN XY: 135148

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.000987

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000496 AC: 723 AN: 1457136 Hom.: 10 Cov.: 35 AF XY: 0.000450 AC XY: 326 AN XY: 725068

Gnomad4 AFR exome AF: 0.0128

Gnomad4 AMR exome AF: 0.00133

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000104

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.0103 AC: 1565 AN: 151830 Hom.: 32 Cov.: 31 AF XY: 0.0104 AC XY: 774 AN XY: 74258

Gnomad4 AFR AF: 0.0353

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00759

Alfa AF: 0.000381 Hom.: 0

Bravo AF: 0.0124

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0393 AC: 173

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00386 AC: 467

EpiCase AF: 0.000872

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.4
DANN	Benign	0.93
DEOGEN2	Benign	0.19	T;.;.;.;.;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.69	T;T;T;T;T;T
MetaRNN	Benign	0.0034	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;L;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.3	N;.;N;N;N;.
REVEL	Benign	0.026
Sift	Benign	0.050	D;.;D;T;D;.
Sift4G	Benign	0.061	T;T;D;T;T;T
Polyphen		0.0020	B;P;B;B;B;B
Vest4		0.20
MVP		0.16
MPC		0.090
ClinPred		0.0044	T
GERP RS		0.74
Varity_R		0.055
gMVP		0.15

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

Other links and lift over

dbSNP: rs11465380; hg19: chr19-7810428;