8-16125965-A-G

Variant names:

• chr8-16125965-A-G
• rs17677191
• NM_138715.3:c.1034-5359T>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.1034-5359T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 152,196 control chromosomes in the GnomAD database, including 252 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 0.045 (252 hom., cov: 33)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 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.1034-5359T>C		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.1088-5359T>C		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.1034-15747T>C		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.1034-5359T>C		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.1088-5359T>C		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.1034-15747T>C		intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6805 AN: 152078 Hom.: 250 Cov.: 33

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.0716

Gnomad AMR AF: 0.0741

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0448 AC: 6821 AN: 152196 Hom.: 252 Cov.: 33 AF XY: 0.0482 AC XY: 3588 AN XY: 74422

African (AFR) AF: 0.0646 AC: 2685 AN: 41544

American (AMR) AF: 0.0746 AC: 1141 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.138 AC: 716 AN: 5172

South Asian (SAS) AF: 0.120 AC: 580 AN: 4814

European-Finnish (FIN) AF: 0.0271 AC: 288 AN: 10614

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0178 AC: 1213 AN: 67978

Other (OTH) AF: 0.0455 AC: 96 AN: 2112

Alfa AF: 0.0320 Hom.: 18

Bravo AF: 0.0489

Asia WGS AF: 0.124 AC: 429 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.71
PhyloP100		-0.20
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: rs17677191; hg19: chr8-15983474;