8-16232964-C-T

Variant names:

• chr8-16232964-C-T
• rs9325782
• ENST00000518026.5:c.29+32209G>A

Variant summary

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

The ENST00000518026.5(MSR1):​c.29+32209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,144 control chromosomes in the GnomAD database, including 60,552 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 0.88 (60552 hom., cov: 31)
• Consequence: MSR1 ENST00000518026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000518026.5	c.29+32209G>A		intron_variant	Intron 4 of 5	4		ENSP00000429498.1

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133458 AN: 152026 Hom.: 60545 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.908

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

GnomAD4 genome AF: 0.878 AC: 133511 AN: 152144 Hom.: 60552 Cov.: 31 AF XY: 0.880 AC XY: 65442 AN XY: 74384

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.992

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.993

Gnomad4 NFE AF: 0.987

Gnomad4 OTH AF: 0.906

Alfa AF: 0.934 Hom.: 14738

Bravo AF: 0.861

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.41
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9325782; hg19: chr8-16090473;