rs381111

Variant names:

• chr8-16188440-G-A
• rs381111
• NM_138715.3:c.-5+4158C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-16188440-G-A
• chr8-16188440-G-C

Variant summary

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

The NM_138715.3(MSR1):​c.-5+4158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,812 control chromosomes in the GnomAD database, including 3,933 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 0.18 (3933 hom., cov: 31)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSR1	NM_138715.3	c.-5+4158C>T		intron_variant	Intron 1 of 9	ENST00000262101.10	NP_619729.1
MSR1	NM_138716.3	c.-5+4158C>T		intron_variant	Intron 1 of 8		NP_619730.1
MSR1	NM_002445.4	c.-5+4158C>T		intron_variant	Intron 1 of 8		NP_002436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10	c.-5+4158C>T		intron_variant	Intron 1 of 9	1	NM_138715.3	ENSP00000262101.5

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27578 AN: 151692 Hom.: 3899 Cov.: 31

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.182 AC: 27671 AN: 151812 Hom.: 3933 Cov.: 31 AF XY: 0.181 AC XY: 13455 AN XY: 74202

African (AFR) AF: 0.392 AC: 16195 AN: 41364

American (AMR) AF: 0.229 AC: 3484 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3468

East Asian (EAS) AF: 0.113 AC: 584 AN: 5158

South Asian (SAS) AF: 0.123 AC: 589 AN: 4804

European-Finnish (FIN) AF: 0.0453 AC: 478 AN: 10544

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.0795 AC: 5404 AN: 67944

Other (OTH) AF: 0.176 AC: 370 AN: 2104

Alfa AF: 0.108 Hom.: 2229

Bravo AF: 0.207

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.7
DANN	Benign	0.72
PhyloP100		1.1
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

Other links and lift over

dbSNP: rs381111; hg19: chr8-16045949;