rs10503579

Variant names:

• chr8-16503393-A-T
• rs10503579
• ENST00000518026.5:c.-180+8454T>A

Variant summary

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

The ENST00000518026.5(MSR1):​c.-180+8454T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 151,234 control chromosomes in the GnomAD database, including 408 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 0.046 (408 hom., cov: 33)
• Consequence: MSR1 ENST00000518026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• 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

LOC101929028 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101929028	XR_007061175.1	n.937-5409T>A		intron_variant	Intron 7 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000518026.5	c.-180+8454T>A		intron_variant	Intron 2 of 5	4		ENSP00000429498.1
MSR1	ENST00000518343.5	n.94-5409T>A		intron_variant	Intron 2 of 5	4
MSR1	ENST00000521876.5	n.70+8454T>A		intron_variant	Intron 1 of 4	5
MSR1	ENST00000522130.1	n.216+8454T>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6903 AN: 151118 Hom.: 409 Cov.: 33

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0316

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

GnomAD4 genome AF: 0.0457 AC: 6905 AN: 151234 Hom.: 408 Cov.: 33 AF XY: 0.0494 AC XY: 3654 AN XY: 73968

African (AFR) AF: 0.0590 AC: 2393 AN: 40576

American (AMR) AF: 0.0486 AC: 743 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.293 AC: 1508 AN: 5150

South Asian (SAS) AF: 0.122 AC: 590 AN: 4820

European-Finnish (FIN) AF: 0.0239 AC: 254 AN: 10620

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0177 AC: 1206 AN: 68012

Other (OTH) AF: 0.0298 AC: 63 AN: 2112

Alfa AF: 0.0285 Hom.: 15

Bravo AF: 0.0498

Asia WGS AF: 0.182 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.7
DANN	Benign	0.57
PhyloP100		0.073

Splicing

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

Other links and lift over

dbSNP: rs10503579; hg19: chr8-16360902;