8-16560861-A-G

Variant names:

• chr8-16560861-A-G
• rs10094727
• ENST00000518026.5:c.-244+6389T>C

Variant summary

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

The ENST00000518026.5(MSR1):​c.-244+6389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,188 control chromosomes in the GnomAD database, including 48,002 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 0.77 (48002 hom., cov: 32)
• Consequence: MSR1 ENST00000518026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.924
• 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

LOC101929028 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518026.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSR1	ENST00000518026.5	TSL:4	c.-244+6389T>C		intron	N/A	ENSP00000429498.1
	MSR1	ENST00000518343.5	TSL:4	n.29+6531T>C		intron	N/A
	MSR1	ENST00000522130.1	TSL:3	n.152+4674T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117594 AN: 152068 Hom.: 47981 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.773 AC: 117655 AN: 152188 Hom.: 48002 Cov.: 32 AF XY: 0.773 AC XY: 57541 AN XY: 74422

African (AFR) AF: 0.506 AC: 21000 AN: 41514

American (AMR) AF: 0.766 AC: 11690 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2954 AN: 3470

East Asian (EAS) AF: 0.597 AC: 3082 AN: 5166

South Asian (SAS) AF: 0.788 AC: 3803 AN: 4826

European-Finnish (FIN) AF: 0.943 AC: 10013 AN: 10620

Middle Eastern (MID) AF: 0.870 AC: 254 AN: 292

European-Non Finnish (NFE) AF: 0.917 AC: 62391 AN: 68028

Other (OTH) AF: 0.809 AC: 1706 AN: 2110

Alfa AF: 0.851 Hom.: 30564

Bravo AF: 0.744

Asia WGS AF: 0.699 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.31
PhyloP100		0.92

Splicing

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

Other links and lift over

dbSNP: rs10094727; hg19: chr8-16418370;