chr8-16552983-T-C

Variant names:

• chr8-16552983-T-C
• rs1526427
• ENST00000518026.5:c.-244+14267A>G

Variant summary

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

The ENST00000518026.5(MSR1):​c.-244+14267A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 152,112 control chromosomes in the GnomAD database, including 706 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 0.053 (706 hom., cov: 31)
• Consequence: MSR1 ENST00000518026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 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

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	ENST00000518026.5	TSL:4	c.-244+14267A>G		intron	N/A	ENSP00000429498.1	E5RI91
	MSR1	ENST00000518343.5	TSL:4	n.29+14409A>G		intron	N/A
	MSR1	ENST00000522130.1	TSL:3	n.152+12552A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8115 AN: 151992 Hom.: 700 Cov.: 31

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.00895

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0568

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

GnomAD4 genome AF: 0.0534 AC: 8128 AN: 152112 Hom.: 706 Cov.: 31 AF XY: 0.0589 AC XY: 4383 AN XY: 74362

African (AFR) AF: 0.0520 AC: 2159 AN: 41546

American (AMR) AF: 0.136 AC: 2075 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.384 AC: 1957 AN: 5098

South Asian (SAS) AF: 0.149 AC: 719 AN: 4814

European-Finnish (FIN) AF: 0.0285 AC: 303 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0115 AC: 783 AN: 67996

Other (OTH) AF: 0.0558 AC: 118 AN: 2116

Alfa AF: 0.0256 Hom.: 235

Bravo AF: 0.0642

Asia WGS AF: 0.220 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.72
PhyloP100		1.2

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: rs1526427;

hg19: chr8-16410492;