rs41341748

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_138715.3(MSR1):c.877C>T(p.Arg293*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00983 in 1,611,828 control chromosomes in the GnomAD database, including 150 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0084 ( 13 hom., cov: 32)

Exomes 𝑓: 0.010 ( 137 hom. )

Consequence

MSR1
NM_138715.3 stop_gained

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:5B:4

Conservation

PhyloP100: 1.22

Publications

66 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 -9 ACMG points.

BP6

Variant 8-16155085-G-A is Benign according to our data. Variant chr8-16155085-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 14357.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00844 (1282/151946) while in subpopulation AMR AF = 0.0131 (200/15214). AF 95% confidence interval is 0.0117. There are 13 homozygotes in GnomAd4. There are 622 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 Unknown gene

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	HGVSp	Effect	Exon Rank	Protein	UniProt
MSR1	NM_138715.3	MANE Select	c.877C>T	p.Arg293*	stop_gained	Exon 6 of 10	NP_619729.1	P21757-1
MSR1	NM_001363744.1		c.931C>T	p.Arg311*	stop_gained	Exon 6 of 10	NP_001350673.1	B4DDJ5
MSR1	NM_138716.3		c.877C>T	p.Arg293*	stop_gained	Exon 6 of 9	NP_619730.1	P21757-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSR1	ENST00000262101.10	TSL:1 MANE Select	c.877C>T	p.Arg293*	stop_gained	Exon 6 of 10	ENSP00000262101.5	P21757-1
MSR1	ENST00000445506.6	TSL:1	c.931C>T	p.Arg311*	stop_gained	Exon 6 of 10	ENSP00000405453.2	B4DDJ5
MSR1	ENST00000355282.6	TSL:1	c.877C>T	p.Arg293*	stop_gained	Exon 5 of 8	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes

AF:

0.00845

AC:

1283

AN:

151830

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.0130

GnomAD2 exomes

AF:

0.00829

AC:

2078

AN:

250570

AF XY:

0.00831

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00926

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.00997

AC:

14556

AN:

1459882

Hom.:

137

Cov.:

AF XY:

0.00984

AC XY:

7144

AN XY:

726302

show subpopulations

African (AFR)

AF:

0.00177

AC:

AN:

33406

American (AMR)

AF:

0.0117

AC:

523

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.0140

AC:

365

AN:

26052

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39664

South Asian (SAS)

AF:

0.000870

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00935

AC:

499

AN:

53344

Middle Eastern (MID)

AF:

0.00538

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0112

AC:

12389

AN:

1110594

Other (OTH)

AF:

0.0102

AC:

613

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

666

1332

1997

2663

3329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.00844

AC:

1282

AN:

151946

Hom.:

Cov.:

AF XY:

0.00838

AC XY:

622

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.00217

AC:

AN:

41492

American (AMR)

AF:

0.0131

AC:

200

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3466

East Asian (EAS)

AF:

0.000388

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0117

AC:

124

AN:

10592

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0117

AC:

794

AN:

67898

Other (OTH)

AF:

0.0128

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

143

214

286

357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0102

Hom.:

Bravo

AF:

0.00835

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00977

AC:

ExAC

AF:

0.00735

AC:

892

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.00979

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Prostate cancer (2)

Barrett esophagus (1)

Hereditary cancer-predisposing syndrome (1)

MSR1-related disorder (1)

X-linked Alport syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.26

Eigen_PC

Benign

-0.032

FATHMM_MKL

Benign

0.076

PhyloP100

1.2

Vest4

0.73

GERP RS

2.8

Mutation Taster

=179/21

disease causing (ClinVar)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over