8-16178960-T-G

Variant names:

• chr8-16178960-T-G
• rs12216764
• NM_138715.3:c.-4-968A>C

Variant summary

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

The NM_138715.3(MSR1):​c.-4-968A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,134 control chromosomes in the GnomAD database, including 4,901 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 0.22 (4901 hom., cov: 32)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 1 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSR1	NM_138715.3	c.-4-968A>C		intron_variant	Intron 1 of 9	ENST00000262101.10	NP_619729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10	c.-4-968A>C		intron_variant	Intron 1 of 9	1	NM_138715.3	ENSP00000262101.5

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33723 AN: 152016 Hom.: 4881 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.222 AC: 33790 AN: 152134 Hom.: 4901 Cov.: 32 AF XY: 0.227 AC XY: 16879 AN XY: 74412

African (AFR) AF: 0.320 AC: 13284 AN: 41474

American (AMR) AF: 0.363 AC: 5540 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3468

East Asian (EAS) AF: 0.542 AC: 2796 AN: 5162

South Asian (SAS) AF: 0.316 AC: 1523 AN: 4822

European-Finnish (FIN) AF: 0.0716 AC: 761 AN: 10622

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.126 AC: 8585 AN: 67990

Other (OTH) AF: 0.244 AC: 515 AN: 2110

Alfa AF: 0.0787 Hom.: 125

Bravo AF: 0.251

Asia WGS AF: 0.405 AC: 1402 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.093
DANN	Benign	0.34
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12216764; hg19: chr8-16036469;