rs1544766

Variant names:

• chr19-7741837-G-A
• rs1544766
• ENST00000678003.1:n.*20C>T

Variant summary

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

The ENST00000678003.1(ENSG00000288669):​n.*20C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 483,978 control chromosomes in the GnomAD database, including 221,705 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 0.93 (66821 hom., cov: 30)
  • Exomes 𝑓: 0.96 (154884 hom.)
• Consequence: ENSG00000288669 ENST00000678003.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 7 publications found

Genes affected

ENSG00000288669 (HGNC:):

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD209	NM_021155.4	c.*1202C>T		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
ENSG00000288669	ENST00000678003.1	n.*20C>T		non_coding_transcript_exon_variant	Exon 2 of 13			ENSP00000504497.1
CD209	ENST00000315599.12	c.*1202C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_021155.4	ENSP00000315477.6
ENSG00000288669	ENST00000678003.1	n.*20C>T		3_prime_UTR_variant	Exon 2 of 13			ENSP00000504497.1

Frequencies

GnomAD3 genomes AF: 0.934 AC: 141850 AN: 151886 Hom.: 66784 Cov.: 30

Gnomad AFR AF: 0.831

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.894

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.948

GnomAD4 exome AF: 0.963 AC: 319813 AN: 331974 Hom.: 154884 Cov.: 3 AF XY: 0.961 AC XY: 178118 AN XY: 185266

African (AFR) AF: 0.830 AC: 6997 AN: 8434

American (AMR) AF: 0.934 AC: 21115 AN: 22610

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 7366 AN: 7394

East Asian (EAS) AF: 0.729 AC: 10891 AN: 14930

South Asian (SAS) AF: 0.916 AC: 47480 AN: 51860

European-Finnish (FIN) AF: 1.00 AC: 30466 AN: 30468

Middle Eastern (MID) AF: 0.983 AC: 1590 AN: 1618

European-Non Finnish (NFE) AF: 0.999 AC: 178854 AN: 179076

Other (OTH) AF: 0.966 AC: 15054 AN: 15584

GnomAD4 genome AF: 0.934 AC: 141942 AN: 152004 Hom.: 66821 Cov.: 30 AF XY: 0.932 AC XY: 69210 AN XY: 74276

African (AFR) AF: 0.830 AC: 34374 AN: 41400

American (AMR) AF: 0.947 AC: 14451 AN: 15266

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

East Asian (EAS) AF: 0.716 AC: 3678 AN: 5136

South Asian (SAS) AF: 0.894 AC: 4306 AN: 4816

European-Finnish (FIN) AF: 1.00 AC: 10580 AN: 10582

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

European-Non Finnish (NFE) AF: 0.998 AC: 67902 AN: 68018

Other (OTH) AF: 0.946 AC: 1997 AN: 2110

Alfa AF: 0.947 Hom.: 9862

Bravo AF: 0.926

Asia WGS AF: 0.818 AC: 2845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.89
DANN	Benign	0.85
PhyloP100		-0.28
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: rs1544766; hg19: chr19-7806723; COSMIC: COSV52660410; COSMIC: COSV52660410;