chr8-16143548-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_138715.3(MSR1):c.1033+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,609,550 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0090 ( 20 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 26 hom. )
Consequence
MSR1
NM_138715.3 intron
NM_138715.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0430
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 8-16143548-A-G is Benign according to our data. Variant chr8-16143548-A-G is described in ClinVar as [Benign]. Clinvar id is 714374.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00898 (1366/152194) while in subpopulation AFR AF= 0.0303 (1260/41538). AF 95% confidence interval is 0.0289. There are 20 homozygotes in gnomad4. There are 647 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1362 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSR1 | NM_138715.3 | c.1033+10T>C | intron_variant | ENST00000262101.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSR1 | ENST00000262101.10 | c.1033+10T>C | intron_variant | 1 | NM_138715.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00896 AC: 1362AN: 152076Hom.: 20 Cov.: 32
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GnomAD3 exomes AF: 0.00236 AC: 590AN: 250066Hom.: 12 AF XY: 0.00178 AC XY: 240AN XY: 135168
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GnomAD4 exome AF: 0.00102 AC: 1486AN: 1457356Hom.: 26 Cov.: 29 AF XY: 0.000900 AC XY: 653AN XY: 725182
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GnomAD4 genome ? AF: 0.00898 AC: 1366AN: 152194Hom.: 20 Cov.: 32 AF XY: 0.00870 AC XY: 647AN XY: 74402
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 26, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at