rs12680619

Variant names:

• chr8-16125232-T-C
• rs12680619
• NM_138715.3:c.1034-4626A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_138715.3(MSR1):​c.1034-4626A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 152,222 control chromosomes in the GnomAD database, including 247 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 0.044 (247 hom., cov: 32)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSR1	NM_138715.3	c.1034-4626A>G		intron_variant	Intron 8 of 9	ENST00000262101.10	NP_619729.1
MSR1	NM_001363744.1	c.1088-4626A>G		intron_variant	Intron 8 of 9		NP_001350673.1
MSR1	NM_138716.3	c.1034-15014A>G		intron_variant	Intron 8 of 8		NP_619730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10	c.1034-4626A>G		intron_variant	Intron 8 of 9	1	NM_138715.3	ENSP00000262101.5

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6733 AN: 152106 Hom.: 245 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.126

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: 0.0443 AC: 6748 AN: 152222 Hom.: 247 Cov.: 32 AF XY: 0.0477 AC XY: 3547 AN XY: 74432

African (AFR) AF: 0.0647 AC: 2688 AN: 41538

American (AMR) AF: 0.0744 AC: 1138 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3472

East Asian (EAS) AF: 0.126 AC: 651 AN: 5162

South Asian (SAS) AF: 0.120 AC: 577 AN: 4816

European-Finnish (FIN) AF: 0.0271 AC: 288 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0178 AC: 1213 AN: 68014

Other (OTH) AF: 0.0455 AC: 96 AN: 2110

Alfa AF: 0.0288 Hom.: 42

Bravo AF: 0.0484

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		-0.50
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: rs12680619; hg19: chr8-15982741;