8-16120602-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_138715.3(MSR1):c.1038A>G(p.Pro346Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 1,549,842 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 17 hom., cov: 21)

Exomes 𝑓: 0.0032 ( 139 hom. )

Consequence

MSR1
NM_138715.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.989

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 8-16120602-T-C is Benign according to our data. Variant chr8-16120602-T-C is described in ClinVar as [Benign]. Clinvar id is 778941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.989 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSR1	NM_138715.3 link	c.1038A>G	p.Pro346Pro	synonymous_variant	Exon 9 of 10	ENST00000262101.10	NP_619729.1	P21757-1
MSR1	NM_001363744.1 link	c.1092A>G	p.Pro364Pro	synonymous_variant	Exon 9 of 10		NP_001350673.1
MSR1	NM_138716.3 link	c.1034-10384A>G		intron_variant	Intron 8 of 8		NP_619730.1	P21757-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MSR1	ENST00000262101.10 link	c.1038A>G	p.Pro346Pro	synonymous_variant	Exon 9 of 10	1	NM_138715.3	ENSP00000262101.5	P21757-1
MSR1	ENST00000445506.6 link	c.1092A>G	p.Pro364Pro	synonymous_variant	Exon 9 of 10	1		ENSP00000405453.2	B4DDJ5
MSR1	ENST00000355282.6 link	c.1034-10384A>G		intron_variant	Intron 7 of 7	1		ENSP00000347430.2	P21757-3
MSR1	ENST00000350896.3 link	c.1034-10384A>G		intron_variant	Intron 8 of 8	5		ENSP00000262100.3	P21757-3

Frequencies

GnomAD3 genomes

AF:

0.00594

AC:

589

AN:

99100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0337

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0852

Gnomad SAS

AF:

0.00217

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000166

Gnomad OTH

AF:

0.0114

GnomAD3 exomes

AF:

0.0103

AC:

2335

AN:

226504

Hom.:

AF XY:

0.00873

AC XY:

1078

AN XY:

123522

show subpopulations

Gnomad AFR exome

AF:

0.00139

Gnomad AMR exome

AF:

0.0333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0749

Gnomad SAS exome

AF:

0.00187

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000579

Gnomad OTH exome

AF:

0.00597

GnomAD4 exome

AF:

0.00316

AC:

4589

AN:

1450726

Hom.:

139

Cov.:

AF XY:

0.00292

AC XY:

2105

AN XY:

721670

show subpopulations

Gnomad4 AFR exome

AF:

0.000642

Gnomad4 AMR exome

AF:

0.0288

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0695

Gnomad4 SAS exome

AF:

0.00180

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000929

Gnomad4 OTH exome

AF:

0.00546

GnomAD4 genome

AF:

0.00594

AC:

589

AN:

99116

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

300

AN XY:

44752

show subpopulations

Gnomad4 AFR

AF:

0.00131

Gnomad4 AMR

AF:

0.0338

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0852

Gnomad4 SAS

AF:

0.00218

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000166

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00334

Hom.:

Asia WGS

AF:

0.0340

AC:

116

AN:

3456

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MSR1-related disorder

Benign:1

Jul 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.36

DANN

Benign

0.45

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over