19-7740410-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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]

ENSG00000288669 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.*2629C>A		3_prime_UTR	Exon 7 of 7	NP_066978.1
	CD209	NR_026692.2		n.3967C>A		non_coding_transcript_exon	Exon 6 of 6
	CD209	NM_001144897.2		c.*2629C>A		3_prime_UTR	Exon 7 of 7	NP_001138369.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD209	ENST00000315599.12	TSL:1 MANE Select	c.*2629C>A		3_prime_UTR	Exon 7 of 7	ENSP00000315477.6
	ENSG00000288669	ENST00000678003.1		n.*290+1157C>A		intron	N/A	ENSP00000504497.1
	ENSG00000288669	ENST00000676543.1		n.70+5108C>A		intron	N/A	ENSP00000503143.1

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

African (AFR) AF: 0.460 AC: 5469 AN: 11892

American (AMR) AF: 0.629 AC: 11375 AN: 18090

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 8542 AN: 14566

East Asian (EAS) AF: 0.263 AC: 7486 AN: 28498

South Asian (SAS) AF: 0.536 AC: 27721 AN: 51690

European-Finnish (FIN) AF: 0.577 AC: 25272 AN: 43806

Middle Eastern (MID) AF: 0.553 AC: 1184 AN: 2140

European-Non Finnish (NFE) AF: 0.559 AC: 151954 AN: 271988

Other (OTH) AF: 0.546 AC: 13688 AN: 25082

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

African (AFR) AF: 0.471 AC: 19496 AN: 41406

American (AMR) AF: 0.608 AC: 9288 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2026 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1338 AN: 5174

South Asian (SAS) AF: 0.519 AC: 2501 AN: 4818

European-Finnish (FIN) AF: 0.568 AC: 5984 AN: 10542

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37926 AN: 67960

Other (OTH) AF: 0.551 AC: 1162 AN: 2110

Alfa AF: 0.541 Hom.: 41942

Bravo AF: 0.529

Asia WGS AF: 0.437 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.76
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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