19-7741982-T-A

Variant names:

• chr19-7741982-T-A
• rs1544767
• NM_021155.4:c.*1057A>T

Variant summary

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

The NM_021155.4(CD209):​c.*1057A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 348,674 control chromosomes in the GnomAD database, including 159,749 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 0.94 (67170 hom., cov: 28)
  • Exomes 𝑓: 0.97 (92579 hom.)
• Consequence: CD209 NM_021155.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 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.*1057A>T		3_prime_UTR	Exon 7 of 7	NP_066978.1
	CD209	NR_026692.2		n.2395A>T		non_coding_transcript_exon	Exon 6 of 6
	CD209	NM_001144897.2		c.*1057A>T		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.*1057A>T		3_prime_UTR	Exon 7 of 7	ENSP00000315477.6
	ENSG00000288669	ENST00000678003.1		n.146-85A>T		intron	N/A	ENSP00000504497.1
	ENSG00000288669	ENST00000678227.1		n.164A>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.937 AC: 142201 AN: 151736 Hom.: 67129 Cov.: 28

Gnomad AFR AF: 0.841

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.893

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.952

GnomAD4 exome AF: 0.968 AC: 190432 AN: 196820 Hom.: 92579 Cov.: 0 AF XY: 0.964 AC XY: 105640 AN XY: 109630

African (AFR) AF: 0.845 AC: 3606 AN: 4268

American (AMR) AF: 0.937 AC: 8317 AN: 8872

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3518 AN: 3530

East Asian (EAS) AF: 0.716 AC: 5138 AN: 7180

South Asian (SAS) AF: 0.919 AC: 31298 AN: 34052

European-Finnish (FIN) AF: 1.00 AC: 24303 AN: 24304

Middle Eastern (MID) AF: 0.983 AC: 1829 AN: 1860

European-Non Finnish (NFE) AF: 0.999 AC: 103673 AN: 103768

Other (OTH) AF: 0.974 AC: 8750 AN: 8986

GnomAD4 genome AF: 0.937 AC: 142300 AN: 151854 Hom.: 67170 Cov.: 28 AF XY: 0.935 AC XY: 69330 AN XY: 74162

African (AFR) AF: 0.840 AC: 34762 AN: 41362

American (AMR) AF: 0.950 AC: 14450 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3452 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3683 AN: 5134

South Asian (SAS) AF: 0.894 AC: 4281 AN: 4790

European-Finnish (FIN) AF: 1.00 AC: 10556 AN: 10558

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67909 AN: 68014

Other (OTH) AF: 0.952 AC: 2007 AN: 2108

Alfa AF: 0.979 Hom.: 40548

Bravo AF: 0.929

Asia WGS AF: 0.822 AC: 2861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.65
DANN	Benign	0.72
PhyloP100		-1.2
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: rs1544767; hg19: chr19-7806868;