8-16279589-T-C

Variant names:

• chr8-16279589-T-C
• rs1383162
• ENST00000518026.5:c.-130-14258A>G

Variant summary

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

The ENST00000518026.5(MSR1):​c.-130-14258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 152,136 control chromosomes in the GnomAD database, including 67,623 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 0.94 (67623 hom., cov: 32)
• Consequence: MSR1 ENST00000518026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 0 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=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000518026.5	c.-130-14258A>G		intron_variant	Intron 3 of 5	4		ENSP00000429498.1
MSR1	ENST00000518343.5	n.359-14258A>G		intron_variant	Intron 4 of 5	4
MSR1	ENST00000521876.5	n.120-14258A>G		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.940 AC: 142828 AN: 152018 Hom.: 67583 Cov.: 32

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.953

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

GnomAD4 genome AF: 0.939 AC: 142925 AN: 152136 Hom.: 67623 Cov.: 32 AF XY: 0.940 AC XY: 69895 AN XY: 74366

African (AFR) AF: 0.812 AC: 33642 AN: 41452

American (AMR) AF: 0.976 AC: 14910 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3456 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5169 AN: 5170

South Asian (SAS) AF: 0.998 AC: 4816 AN: 4826

European-Finnish (FIN) AF: 0.969 AC: 10288 AN: 10614

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67512 AN: 68012

Other (OTH) AF: 0.953 AC: 2013 AN: 2112

Alfa AF: 0.974 Hom.: 26378

Bravo AF: 0.934

Asia WGS AF: 0.986 AC: 3428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.024
DANN	Benign	0.40
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs1383162; hg19: chr8-16137098;