NM_138715.3:c.1034-1184A>G

Variant names:

• chr8-16121790-T-C
• rs12114599
• NM_138715.3:c.1034-1184A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138715.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSR1	NM_138715.3	MANE Select	c.1034-1184A>G		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.1088-1184A>G		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.1034-11572A>G		intron	N/A	NP_619730.1	P21757-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSR1	ENST00000262101.10	TSL:1 MANE Select	c.1034-1184A>G		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.1088-1184A>G		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.1034-11572A>G		intron	N/A	ENSP00000347430.2	P21757-3

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

African (AFR) AF: 0.0551 AC: 2286 AN: 41474

American (AMR) AF: 0.102 AC: 1556 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3472

East Asian (EAS) AF: 0.127 AC: 658 AN: 5168

South Asian (SAS) AF: 0.179 AC: 863 AN: 4814

European-Finnish (FIN) AF: 0.0521 AC: 544 AN: 10442

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.0349 AC: 2364 AN: 67822

Other (OTH) AF: 0.0683 AC: 144 AN: 2108

Alfa AF: 0.0419 Hom.: 37

Bravo AF: 0.0591

Asia WGS AF: 0.152 AC: 519 AN: 3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.70
PhyloP100		0.26
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: rs12114599; hg19: chr8-15979299;