19-7740410-G-T

Variant names:

• chr19-7740410-G-T
• rs11465421
• NM_021155.4:c.*2629C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021155.4(CD209):​c.*2629C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 619,714 control chromosomes in the GnomAD database, including 91,533 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 0.53 (21507 hom., cov: 32)
  • Exomes 𝑓: 0.54 (70026 hom.)
• Consequence: CD209 NM_021155.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD209	NM_021155.4	c.*2629C>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000315599.12	NP_066978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD209	ENST00000315599	c.*2629C>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_021155.4	ENSP00000315477.6
ENSG00000288669	ENST00000678003.1	n.*290+1157C>A		intron_variant	Intron 2 of 12			ENSP00000504497.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80247 AN: 151844 Hom.: 21480 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.550

GnomAD4 exome AF: 0.540 AC: 252691 AN: 467752 Hom.: 70026 Cov.: 4 AF XY: 0.540 AC XY: 136538 AN XY: 252646

Gnomad4 AFR exome AF: 0.460

Gnomad4 AMR exome AF: 0.629

Gnomad4 ASJ exome AF: 0.586

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.536

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.559

Gnomad4 OTH exome AF: 0.546

GnomAD4 genome AF: 0.529 AC: 80324 AN: 151962 Hom.: 21507 Cov.: 32 AF XY: 0.527 AC XY: 39115 AN XY: 74246

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.551

Alfa AF: 0.544 Hom.: 29090

Bravo AF: 0.529

Asia WGS AF: 0.437 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.76

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: rs11465421; hg19: chr19-7805296; COSMIC: COSV52659436; COSMIC: COSV52659436;