rs7252229

Variant names:

• chr19-7747295-G-C
• rs7252229
• NM_021155.4:c.106+11C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021155.4(CD209):​c.106+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,510 control chromosomes in the GnomAD database, including 20,192 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4428 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15764 hom.)
• Consequence: CD209 NM_021155.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021155.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD209	NM_021155.4	MANE Select	c.106+11C>G		intron	N/A	NP_066978.1
	CD209	NM_001144897.2		c.106+11C>G		intron	N/A	NP_001138369.1
	CD209	NM_001144896.2		c.106+11C>G		intron	N/A	NP_001138368.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD209	ENST00000315599.12	TSL:1 MANE Select	c.106+11C>G		intron	N/A	ENSP00000315477.6
	CD209	ENST00000354397.10	TSL:1	c.106+11C>G		intron	N/A	ENSP00000346373.5
	CD209	ENST00000315591.12	TSL:1	c.106+11C>G		intron	N/A	ENSP00000315407.7

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31833 AN: 152042 Hom.: 4431 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.141 AC: 35475 AN: 251434 AF XY: 0.137

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.0917

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.0717

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.138 AC: 202099 AN: 1461350 Hom.: 15764 Cov.: 33 AF XY: 0.137 AC XY: 99385 AN XY: 727012

African (AFR) AF: 0.415 AC: 13895 AN: 33468

American (AMR) AF: 0.0980 AC: 4382 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3785 AN: 26128

East Asian (EAS) AF: 0.0561 AC: 2225 AN: 39696

South Asian (SAS) AF: 0.113 AC: 9737 AN: 86242

European-Finnish (FIN) AF: 0.141 AC: 7511 AN: 53420

Middle Eastern (MID) AF: 0.180 AC: 1040 AN: 5764

European-Non Finnish (NFE) AF: 0.135 AC: 150566 AN: 1111528

Other (OTH) AF: 0.148 AC: 8958 AN: 60384

GnomAD4 genome AF: 0.209 AC: 31840 AN: 152160 Hom.: 4428 Cov.: 33 AF XY: 0.207 AC XY: 15406 AN XY: 74406

African (AFR) AF: 0.402 AC: 16670 AN: 41448

American (AMR) AF: 0.137 AC: 2095 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3472

East Asian (EAS) AF: 0.0675 AC: 350 AN: 5186

South Asian (SAS) AF: 0.116 AC: 559 AN: 4826

European-Finnish (FIN) AF: 0.143 AC: 1515 AN: 10606

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9371 AN: 68012

Other (OTH) AF: 0.182 AC: 384 AN: 2112

Alfa AF: 0.171 Hom.: 483

Bravo AF: 0.217

Asia WGS AF: 0.110 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.52
DANN	Benign	0.45
PhyloP100		-0.94
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7252229; hg19: chr19-7812181; COSMIC: COSV52654061; COSMIC: COSV52654061;