dbSNP rs3747531: MSR1:p.Pro275Ala (chr8-16155139-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_138715.3(MSR1):c.823C>G(p.Pro275Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0799 in 1,609,930 control chromosomes in the GnomAD database, including 9,085 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 0.084 ( 844 hom., cov: 32)

Exomes 𝑓: 0.080 ( 8241 hom. )

Consequence

MSR1
NM_138715.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.97

Publications

54 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002927959).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSR1	NM_138715.3 link	c.823C>G	p.Pro275Ala	missense_variant	Exon 6 of 10	ENST00000262101.10	NP_619729.1	P21757-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10 link	c.823C>G	p.Pro275Ala	missense_variant	Exon 6 of 10	1	NM_138715.3	ENSP00000262101.5		P21757-1

Frequencies

GnomAD3 genomes

AF:

0.0839

AC:

12734

AN:

151788

Hom.:

847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0765

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.0528

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.0224

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.0554

Gnomad OTH

AF:

0.0922

GnomAD2 exomes

AF:

0.113

AC:

28231

AN:

249136

AF XY:

0.111

show subpopulations

Gnomad AFR exome

AF:

0.0742

Gnomad AMR exome

AF:

0.236

Gnomad ASJ exome

AF:

0.0469

Gnomad EAS exome

AF:

0.331

Gnomad FIN exome

AF:

0.0211

Gnomad NFE exome

AF:

0.0530

Gnomad OTH exome

AF:

0.0825

GnomAD4 exome

AF:

0.0795

AC:

115935

AN:

1458024

Hom.:

8241

Cov.:

AF XY:

0.0817

AC XY:

59287

AN XY:

725414

show subpopulations

African (AFR)

AF:

0.0726

AC:

2420

AN:

33352

American (AMR)

AF:

0.223

AC:

9910

AN:

44508

Ashkenazi Jewish (ASJ)

AF:

0.0489

AC:

1273

AN:

26028

East Asian (EAS)

AF:

0.375

AC:

14875

AN:

39616

South Asian (SAS)

AF:

0.179

AC:

15403

AN:

86086

European-Finnish (FIN)

AF:

0.0221

AC:

1176

AN:

53282

Middle Eastern (MID)

AF:

0.0714

AC:

411

AN:

5754

European-Non Finnish (NFE)

AF:

0.0588

AC:

65266

AN:

1109230

Other (OTH)

AF:

0.0864

AC:

5201

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

4622

9243

13865

18486

23108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2840

5680

8520

11360

14200

<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:

0.0838

AC:

12737

AN:

151906

Hom.:

844

Cov.:

AF XY:

0.0887

AC XY:

6585

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.0765

AC:

3172

AN:

41488

American (AMR)

AF:

0.153

AC:

2321

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.0528

AC:

183

AN:

3464

East Asian (EAS)

AF:

0.338

AC:

1741

AN:

5146

South Asian (SAS)

AF:

0.203

AC:

975

AN:

4804

European-Finnish (FIN)

AF:

0.0224

AC:

238

AN:

10606

Middle Eastern (MID)

AF:

0.0479

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0554

AC:

3760

AN:

67892

Other (OTH)

AF:

0.0913

AC:

192

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

555

1110

1665

2220

2775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.0610

Hom.:

381

Bravo

AF:

0.0941

TwinsUK

AF:

0.0558

AC:

207

ALSPAC

AF:

0.0649

AC:

250

ESP6500AA

AF:

0.0869

AC:

383

ESP6500EA

AF:

0.0609

AC:

524

ExAC

AF:

0.108

AC:

13155

Asia WGS

AF:

0.224

AC:

777

AN:

3478

EpiCase

AF:

0.0581

EpiControl

AF:

0.0603

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

.;T;.;.;.;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.31

T;T;T;.;T;T

MetaRNN

Benign

0.0029

T;T;T;T;T;T

MetaSVM

Benign

-1.6

MutationAssessor

Benign

1.8

L;L;.;L;.;L

PhyloP100

5.0

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.7

D;D;D;D;D;D

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;.;D

Vest4

0.47

MPC

0.015

ClinPred

0.017

GERP RS

4.9

Varity_R

0.27

gMVP

0.29

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over