8-16232964-C-T

Position:

• chr8-16232964-C-T

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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSR1	ENST00000518026.5	c.29+32209G>A		intron_variant		4

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;