Variant rs3747531 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MSR1	NM_138715.3 linkuse as main transcript	c.823C>G	p.Pro275Ala	missense_variant	6/10	ENST00000262101.10	NP_619729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10 linkuse as main transcript	c.823C>G	p.Pro275Ala	missense_variant	6/10	1	NM_138715.3	ENSP00000262101	P1	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

GnomAD3 exomes

AF:

0.113

AC:

28231

AN:

249136

Hom.:

2817

AF XY:

0.111

AC XY:

14991

AN XY:

134684

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 SAS exome

AF:

0.182

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

Gnomad4 AFR exome

AF:

0.0726

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.0489

Gnomad4 EAS exome

AF:

0.375

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.0221

Gnomad4 NFE exome

AF:

0.0588

Gnomad4 OTH exome

AF:

0.0864

GnomAD4 genome

AF:

0.0838

AC:

12737

AN:

151906

Hom.:

844

Cov.:

AF XY:

0.0887

AC XY:

6585

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.0765

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.0528

Gnomad4 EAS

AF:

0.338

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.0224

Gnomad4 NFE

AF:

0.0554

Gnomad4 OTH

AF:

0.0913

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

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

MutationTaster

Benign

0.0097

P;P;P;P;P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over