Genetic Variant MSR1:c.1034-20_1034-11dupTTTTTTTTTT (chr8-16120616-T-TAAAAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_138715.3(MSR1):c.1034-20_1034-11dupTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000090 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

MSR1
NM_138715.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.140

Publications

0 publications found

Variant links:

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 esophagus
Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

MSR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MSR1	NM_138715.3	MANE Select	c.1034-20_1034-11dupTTTTTTTTTT	intron	N/A	NP_619729.1	P21757-1
MSR1	NM_001363744.1		c.1088-20_1088-11dupTTTTTTTTTT	intron	N/A	NP_001350673.1	B4DDJ5
MSR1	NM_138716.3		c.1034-10408_1034-10399dupTTTTTTTTTT	intron	N/A	NP_619730.1	P21757-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MSR1	ENST00000262101.10	TSL:1 MANE Select	c.1034-11_1034-10insTTTTTTTTTT	intron	N/A	ENSP00000262101.5	P21757-1
MSR1	ENST00000445506.6	TSL:1	c.1088-11_1088-10insTTTTTTTTTT	intron	N/A	ENSP00000405453.2	B4DDJ5
MSR1	ENST00000355282.6	TSL:1	c.1034-10399_1034-10398insTTTTTTTTTT	intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes

AF:

0.000236

AC:

AN:

63504

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000481

Gnomad ASJ

AF:

0.00101

Gnomad EAS

AF:

0.000959

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000171

Gnomad OTH

AF:

0.00131

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000899

AC:

102

AN:

1134536

Hom.:

Cov.:

AF XY:

0.0000997

AC XY:

AN XY:

561522

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000891

AC:

AN:

22446

American (AMR)

AF:

0.000180

AC:

AN:

22284

Ashkenazi Jewish (ASJ)

AF:

0.0000511

AC:

AN:

19566

East Asian (EAS)

AF:

0.000863

AC:

AN:

27812

South Asian (SAS)

AF:

0.000199

AC:

AN:

60398

European-Finnish (FIN)

AF:

0.0000761

AC:

AN:

26270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3052

European-Non Finnish (NFE)

AF:

0.0000562

AC:

AN:

906666

Other (OTH)

AF:

0.000130

AC:

AN:

46042

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000673572), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.391

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000236

AC:

AN:

63506

Hom.:

Cov.:

AF XY:

0.000315

AC XY:

AN XY:

28564

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

16466

American (AMR)

AF:

0.000481

AC:

AN:

4160

Ashkenazi Jewish (ASJ)

AF:

0.00101

AC:

AN:

1986

East Asian (EAS)

AF:

0.000961

AC:

AN:

2082

South Asian (SAS)

AF:

0.00

AC:

AN:

1490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000171

AC:

AN:

35068

Other (OTH)

AF:

0.00131

AC:

AN:

766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over