8-16120616-TAAAAAAAAAAAAAAAA-TAAAAAA
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_138715.3(MSR1):c.1034-20_1034-11delTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000696 in 1,134,444 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000070 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MSR1
NM_138715.3 intron
NM_138715.3 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.86
Publications
0 publications found
Genes affected
MSR1 (HGNC:7376): (macrophage scavenger receptor 1) This gene encodes the class A macrophage scavenger receptors, which include three different types (1, 2, 3) generated by alternative splicing of this gene. These receptors or isoforms are macrophage-specific trimeric integral membrane glycoproteins and have been implicated in many macrophage-associated physiological and pathological processes including atherosclerosis, Alzheimer's disease, and host defense. The isoforms type 1 and type 2 are functional receptors and are able to mediate the endocytosis of modified low density lipoproteins (LDLs). The isoform type 3 does not internalize modified LDL (acetyl-LDL) despite having the domain shown to mediate this function in the types 1 and 2 isoforms. It has an altered intracellular processing and is trapped within the endoplasmic reticulum, making it unable to perform endocytosis. The isoform type 3 can inhibit the function of isoforms type 1 and type 2 when co-expressed, indicating a dominant negative effect and suggesting a mechanism for regulation of scavenger receptor activity in macrophages. [provided by RefSeq, Jul 2008]
MSR1 Gene-Disease associations (from GenCC):
- Barrett esophagusInheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_138715.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MSR1 | MANE Select | c.1034-20_1034-11delTTTTTTTTTT | intron | N/A | NP_619729.1 | P21757-1 | |||
| MSR1 | c.1088-20_1088-11delTTTTTTTTTT | intron | N/A | NP_001350673.1 | B4DDJ5 | ||||
| MSR1 | c.1034-10408_1034-10399delTTTTTTTTTT | intron | N/A | NP_619730.1 | P21757-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MSR1 | TSL:1 MANE Select | c.1034-20_1034-11delTTTTTTTTTT | intron | N/A | ENSP00000262101.5 | P21757-1 | |||
| MSR1 | TSL:1 | c.1088-20_1088-11delTTTTTTTTTT | intron | N/A | ENSP00000405453.2 | B4DDJ5 | |||
| MSR1 | TSL:1 | c.1034-10408_1034-10399delTTTTTTTTTT | intron | N/A | ENSP00000347430.2 | P21757-3 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 63504Hom.: 0 Cov.: 0
GnomAD3 genomes
AF:
AC:
0
AN:
63504
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000696 AC: 79AN: 1134444Hom.: 0 AF XY: 0.0000784 AC XY: 44AN XY: 561478 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
79
AN:
1134444
Hom.:
AF XY:
AC XY:
44
AN XY:
561478
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
22446
American (AMR)
AF:
AC:
5
AN:
22286
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
19560
East Asian (EAS)
AF:
AC:
0
AN:
27820
South Asian (SAS)
AF:
AC:
2
AN:
60404
European-Finnish (FIN)
AF:
AC:
5
AN:
26268
Middle Eastern (MID)
AF:
AC:
0
AN:
3050
European-Non Finnish (NFE)
AF:
AC:
62
AN:
906578
Other (OTH)
AF:
AC:
3
AN:
46032
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.287
Heterozygous variant carriers
0
8
15
23
30
38
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
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>80
Age
GnomAD4 genome 0.00 AC: 0AN: 63504Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 28554
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
63504
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
28554
African (AFR)
AF:
AC:
0
AN:
16444
American (AMR)
AF:
AC:
0
AN:
4160
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
1986
East Asian (EAS)
AF:
AC:
0
AN:
2086
South Asian (SAS)
AF:
AC:
0
AN:
1506
European-Finnish (FIN)
AF:
AC:
0
AN:
938
Middle Eastern (MID)
AF:
AC:
0
AN:
58
European-Non Finnish (NFE)
AF:
AC:
0
AN:
35072
Other (OTH)
AF:
AC:
0
AN:
762
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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