rs868875

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000598879.5(CLEC4M):​n.857A>G 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 0.286 in 1,590,608 control chromosomes in the GnomAD database, including 66,813 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 0.26 ( 5590 hom., cov: 32)
Exomes 𝑓: 0.29 ( 61223 hom. )

Consequence

CLEC4M
ENST00000598879.5 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

Publications

26 publications found
Variant links:
Genes affected
CLEC4M (HGNC:13523): (C-type lectin domain family 4 member M) 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 tuberculosis mycobacteria, and viruses including Ebola, hepatitis C, HIV-1, influenza A, West Nile virus 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 of variable length, 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, CD209 (Gene ID: 30835), also known as DC-SIGN. The two genes differ in viral recognition and expression patterns, with this gene showing high expression in endothelial cells of the liver, lymph node and placenta. Polymorphisms in the tandem repeat neck domain are associated with resistance to SARS infection. [provided by RefSeq, May 2020]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.0).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLEC4MNM_014257.5 linkc.784+73A>G intron_variant Intron 4 of 6 ENST00000327325.10 NP_055072.3 Q9H2X3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLEC4MENST00000327325.10 linkc.784+73A>G intron_variant Intron 4 of 6 1 NM_014257.5 ENSP00000316228.4 Q9H2X3-1

Frequencies

GnomAD3 genomes
AF:
0.255
AC:
38787
AN:
152036
Hom.:
5573
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.132
Gnomad AMI
AF:
0.515
Gnomad AMR
AF:
0.338
Gnomad ASJ
AF:
0.205
Gnomad EAS
AF:
0.186
Gnomad SAS
AF:
0.207
Gnomad FIN
AF:
0.310
Gnomad MID
AF:
0.278
Gnomad NFE
AF:
0.310
Gnomad OTH
AF:
0.268
GnomAD2 exomes
AF:
0.279
AC:
62588
AN:
224536
AF XY:
0.279
show subpopulations
Gnomad AFR exome
AF:
0.133
Gnomad AMR exome
AF:
0.334
Gnomad ASJ exome
AF:
0.194
Gnomad EAS exome
AF:
0.188
Gnomad FIN exome
AF:
0.309
Gnomad NFE exome
AF:
0.317
Gnomad OTH exome
AF:
0.294
GnomAD4 exome
AF:
0.289
AC:
416008
AN:
1438454
Hom.:
61223
Cov.:
54
AF XY:
0.288
AC XY:
205690
AN XY:
713024
show subpopulations
African (AFR)
AF:
0.124
AC:
4098
AN:
33024
American (AMR)
AF:
0.334
AC:
14002
AN:
41890
Ashkenazi Jewish (ASJ)
AF:
0.192
AC:
4851
AN:
25330
East Asian (EAS)
AF:
0.179
AC:
7058
AN:
39352
South Asian (SAS)
AF:
0.214
AC:
18027
AN:
84224
European-Finnish (FIN)
AF:
0.301
AC:
14861
AN:
49354
Middle Eastern (MID)
AF:
0.250
AC:
1405
AN:
5618
European-Non Finnish (NFE)
AF:
0.305
AC:
335683
AN:
1100146
Other (OTH)
AF:
0.269
AC:
16023
AN:
59516
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
17353
34705
52058
69410
86763
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10866
21732
32598
43464
54330
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.255
AC:
38840
AN:
152154
Hom.:
5590
Cov.:
32
AF XY:
0.255
AC XY:
18987
AN XY:
74390
show subpopulations
African (AFR)
AF:
0.133
AC:
5506
AN:
41530
American (AMR)
AF:
0.339
AC:
5174
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
0.205
AC:
712
AN:
3468
East Asian (EAS)
AF:
0.187
AC:
968
AN:
5182
South Asian (SAS)
AF:
0.208
AC:
1003
AN:
4832
European-Finnish (FIN)
AF:
0.310
AC:
3282
AN:
10584
Middle Eastern (MID)
AF:
0.279
AC:
82
AN:
294
European-Non Finnish (NFE)
AF:
0.310
AC:
21072
AN:
67974
Other (OTH)
AF:
0.270
AC:
571
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1452
2905
4357
5810
7262
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
390
780
1170
1560
1950
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.292
Hom.:
30771
Bravo
AF:
0.254
Asia WGS
AF:
0.198
AC:
689
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.045
DANN
Benign
0.30
PhyloP100
-1.8
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

Publications

Other links and lift over

dbSNP: rs868875; hg19: chr19-7831166; API