8-16193362-C-G

Variant names:

• chr8-16193362-C-G
• rs28491433
• ENST00000518960.5:c.-4-15370G>C

Variant summary

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

The ENST00000518960.5(MSR1):​c.-4-15370G>C 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 151,360 control chromosomes in the GnomAD database, including 3,894 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 (3894 hom., cov: 29)
• Consequence: MSR1 ENST00000518960.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518960.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSR1	ENST00000518960.5	TSL:3	c.-4-15370G>C		intron	N/A	ENSP00000427905.1	E5RFW8
	MSR1	ENST00000518026.5	TSL:4	c.30-15370G>C		intron	N/A	ENSP00000429498.1	E5RI91

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27487 AN: 151238 Hom.: 3859 Cov.: 29

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.182 AC: 27580 AN: 151360 Hom.: 3894 Cov.: 29 AF XY: 0.181 AC XY: 13402 AN XY: 73950

African (AFR) AF: 0.391 AC: 16134 AN: 41222

American (AMR) AF: 0.230 AC: 3491 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 424 AN: 3458

East Asian (EAS) AF: 0.112 AC: 561 AN: 5012

South Asian (SAS) AF: 0.121 AC: 578 AN: 4790

European-Finnish (FIN) AF: 0.0450 AC: 473 AN: 10508

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.0798 AC: 5414 AN: 67878

Other (OTH) AF: 0.174 AC: 366 AN: 2098

Alfa AF: 0.133 Hom.: 325

Bravo AF: 0.208

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.90
DANN	Benign	0.65
PhyloP100		-0.38

Splicing

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: rs28491433;

hg19: chr8-16050871;