Genetic Variant NM_138715.3:c.1034-11dupT (chr8-16120616-T-TA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_138715.3(MSR1):c.1034-11dupT 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 0.038 ( 120 hom., cov: 0)

Exomes 𝑓: 0.0082 ( 1 hom. )

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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

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.1034-11dupT	intron	N/A	NP_619729.1	P21757-1
MSR1	NM_001363744.1		c.1088-11dupT	intron	N/A	NP_001350673.1	B4DDJ5
MSR1	NM_138716.3		c.1034-10399dupT	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_1034-10insT	intron	N/A	ENSP00000262101.5	P21757-1
MSR1	ENST00000445506.6	TSL:1	c.1088-11_1088-10insT	intron	N/A	ENSP00000405453.2	B4DDJ5
MSR1	ENST00000355282.6	TSL:1	c.1034-10399_1034-10398insT	intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes

AF:

0.0383

AC:

2431

AN:

63446

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.00201

Gnomad EAS

AF:

0.00722

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.0161

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0223

GnomAD4 exome

AF:

0.00824

AC:

9277

AN:

1125776

Hom.:

Cov.:

AF XY:

0.00835

AC XY:

4653

AN XY:

556964

show subpopulations

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

African (AFR)

AF:

0.0447

AC:

974

AN:

21780

American (AMR)

AF:

0.0211

AC:

462

AN:

21888

Ashkenazi Jewish (ASJ)

AF:

0.00674

AC:

131

AN:

19446

East Asian (EAS)

AF:

0.0110

AC:

302

AN:

27512

South Asian (SAS)

AF:

0.0157

AC:

931

AN:

59416

European-Finnish (FIN)

AF:

0.0123

AC:

320

AN:

26018

Middle Eastern (MID)

AF:

0.0109

AC:

AN:

3022

European-Non Finnish (NFE)

AF:

0.00629

AC:

5665

AN:

901104

Other (OTH)

AF:

0.0101

AC:

459

AN:

45590

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.297

Heterozygous variant carriers

674

1347

2021

2694

3368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

224

448

672

896

1120

<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:

0.0383

AC:

2433

AN:

63448

Hom.:

120

Cov.:

AF XY:

0.0386

AC XY:

1102

AN XY:

28544

show subpopulations

African (AFR)

AF:

0.112

AC:

1848

AN:

16444

American (AMR)

AF:

0.0272

AC:

113

AN:

4162

Ashkenazi Jewish (ASJ)

AF:

0.00201

AC:

AN:

1986

East Asian (EAS)

AF:

0.00723

AC:

AN:

2074

South Asian (SAS)

AF:

0.0154

AC:

AN:

1490

European-Finnish (FIN)

AF:

0.0161

AC:

AN:

934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0114

AC:

398

AN:

35042

Other (OTH)

AF:

0.0222

AC:

AN:

766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

181

272

362

453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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