rs414580

Variant names:

• chr8-16177793-T-A
• rs414580
• NM_138715.3:c.103+93A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-16177793-T-A
• chr8-16177793-T-C
• chr8-16177793-T-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.103+93A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 970,344 control chromosomes in the GnomAD database, including 24,051 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 (4751 hom., cov: 32)
  • Exomes 𝑓: 0.18 (19300 hom.)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSR1	NM_138715.3	c.103+93A>T		intron_variant	Intron 2 of 9	ENST00000262101.10	NP_619729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10	c.103+93A>T		intron_variant	Intron 2 of 9	1	NM_138715.3	ENSP00000262101.5

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33084 AN: 151934 Hom.: 4732 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 0.178 AC: 145819 AN: 818292 Hom.: 19300 AF XY: 0.181 AC XY: 77261 AN XY: 427570

African (AFR) AF: 0.319 AC: 6605 AN: 20708

American (AMR) AF: 0.447 AC: 16361 AN: 36598

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 3731 AN: 21462

East Asian (EAS) AF: 0.567 AC: 19657 AN: 34696

South Asian (SAS) AF: 0.289 AC: 20023 AN: 69282

European-Finnish (FIN) AF: 0.0702 AC: 3271 AN: 46626

Middle Eastern (MID) AF: 0.252 AC: 1142 AN: 4532

European-Non Finnish (NFE) AF: 0.124 AC: 67457 AN: 545470

Other (OTH) AF: 0.195 AC: 7572 AN: 38918

GnomAD4 genome AF: 0.218 AC: 33150 AN: 152052 Hom.: 4751 Cov.: 32 AF XY: 0.223 AC XY: 16542 AN XY: 74324

African (AFR) AF: 0.311 AC: 12879 AN: 41450

American (AMR) AF: 0.359 AC: 5476 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3466

East Asian (EAS) AF: 0.541 AC: 2784 AN: 5148

South Asian (SAS) AF: 0.315 AC: 1520 AN: 4818

European-Finnish (FIN) AF: 0.0714 AC: 757 AN: 10608

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8445 AN: 67992

Other (OTH) AF: 0.241 AC: 509 AN: 2114

Alfa AF: 0.0516 Hom.: 58

Bravo AF: 0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.40
PhyloP100		-0.52
PromoterAI		-0.0020	Neutral
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: rs414580; hg19: chr8-16035302;