rs406652

Variant names:

• chr8-16184998-G-C
• rs406652
• NM_138715.3:c.-4-7006C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138715.3(MSR1):​c.-4-7006C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,004 control chromosomes in the GnomAD database, including 1,834 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 0.14 (1834 hom., cov: 32)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSR1	NM_138715.3	MANE Select	c.-4-7006C>G		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.50+1161C>G		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.-4-7006C>G		intron	N/A	NP_619730.1	P21757-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSR1	ENST00000262101.10	TSL:1 MANE Select	c.-4-7006C>G		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.50+1161C>G		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000381998.8	TSL:1	c.-4-7006C>G		intron	N/A	ENSP00000371428.4	P21757-2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20791 AN: 151886 Hom.: 1821 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0798

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20840 AN: 152004 Hom.: 1834 Cov.: 32 AF XY: 0.137 AC XY: 10151 AN XY: 74314

African (AFR) AF: 0.230 AC: 9548 AN: 41436

American (AMR) AF: 0.213 AC: 3240 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3470

East Asian (EAS) AF: 0.113 AC: 580 AN: 5146

South Asian (SAS) AF: 0.128 AC: 616 AN: 4818

European-Finnish (FIN) AF: 0.0521 AC: 552 AN: 10602

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0799 AC: 5428 AN: 67976

Other (OTH) AF: 0.150 AC: 318 AN: 2114

Alfa AF: 0.108 Hom.: 169

Bravo AF: 0.155

Asia WGS AF: 0.157 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		-0.033
Mutation Taster		=100/0	polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs406652;

hg19: chr8-16042507;