rs12114599

Positions:

• chr8-16121790-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138715.3(MSR1):​c.1034-1184A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0572 in 151,740 control chromosomes in the GnomAD database, including 356 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 0.057 (356 hom., cov: 32)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSR1	NM_138715.3	c.1034-1184A>G		intron_variant		ENST00000262101.10	NP_619729.1
MSR1	NM_001363744.1	c.1088-1184A>G		intron_variant			NP_001350673.1
MSR1	NM_138716.3	c.1034-11572A>G		intron_variant			NP_619730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10	c.1034-1184A>G		intron_variant		1	NM_138715.3	ENSP00000262101	P1

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8662 AN: 151624 Hom.: 353 Cov.: 32

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0666

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

GnomAD4 genome AF: 0.0572 AC: 8686 AN: 151740 Hom.: 356 Cov.: 32 AF XY: 0.0622 AC XY: 4616 AN XY: 74174

Gnomad4 AFR AF: 0.0551

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.0349

Gnomad4 OTH AF: 0.0683

Alfa AF: 0.0415 Hom.: 35

Bravo AF: 0.0591

Asia WGS AF: 0.152 AC: 519 AN: 3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12114599; hg19: chr8-15979299;