rs381111

Positions:

• chr8-16188440-G-A
• chr8-16188440-G-C

Variant summary

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

The NM_138715.3(MSR1):​c.-5+4158C>T 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 151,812 control chromosomes in the GnomAD database, including 3,933 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 (3933 hom., cov: 31)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSR1	NM_138715.3	c.-5+4158C>T		intron_variant		ENST00000262101.10	NP_619729.1
MSR1	NM_138716.3	c.-5+4158C>T		intron_variant			NP_619730.1
MSR1	NM_002445.4	c.-5+4158C>T		intron_variant			NP_002436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10	c.-5+4158C>T		intron_variant		1	NM_138715.3	ENSP00000262101.5

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27578 AN: 151692 Hom.: 3899 Cov.: 31

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.182 AC: 27671 AN: 151812 Hom.: 3933 Cov.: 31 AF XY: 0.181 AC XY: 13455 AN XY: 74202

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0453

Gnomad4 NFE AF: 0.0795

Gnomad4 OTH AF: 0.176

Alfa AF: 0.0945 Hom.: 1166

Bravo AF: 0.207

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.7
DANN	Benign	0.72

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: rs381111; hg19: chr8-16045949;