8-16109569-C-T

Variant names:

• chr8-16109569-C-T
• rs918
• NM_138715.3:c.*516G>A

Variant summary

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

The ENST00000262101.10(MSR1):​c.*516G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 165,536 control chromosomes in the GnomAD database, including 890 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 0.091 (826 hom., cov: 32)
  • Exomes 𝑓: 0.078 (64 hom.)
• Consequence: MSR1 ENST00000262101.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262101.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSR1	NM_138715.3	MANE Select	c.*516G>A		3_prime_UTR	Exon 10 of 10	NP_619729.1
	MSR1	NM_001363744.1		c.*516G>A		3_prime_UTR	Exon 10 of 10	NP_001350673.1
	MSR1	NM_138716.3		c.*516G>A		3_prime_UTR	Exon 9 of 9	NP_619730.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSR1	ENST00000262101.10	TSL:1 MANE Select	c.*516G>A		3_prime_UTR	Exon 10 of 10	ENSP00000262101.5
	MSR1	ENST00000350896.3	TSL:5	c.*516G>A		3_prime_UTR	Exon 9 of 9	ENSP00000262100.3

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13784 AN: 151992 Hom.: 824 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0544

Gnomad OTH AF: 0.0852

GnomAD4 exome AF: 0.0779 AC: 1046 AN: 13424 Hom.: 64 Cov.: 0 AF XY: 0.0763 AC XY: 548 AN XY: 7182

African (AFR) AF: 0.276 AC: 16 AN: 58

American (AMR) AF: 0.121 AC: 275 AN: 2268

Ashkenazi Jewish (ASJ) AF: 0.0154 AC: 2 AN: 130

East Asian (EAS) AF: 0.141 AC: 114 AN: 806

South Asian (SAS) AF: 0.117 AC: 208 AN: 1784

European-Finnish (FIN) AF: 0.0164 AC: 5 AN: 304

Middle Eastern (MID) AF: 0.0714 AC: 1 AN: 14

European-Non Finnish (NFE) AF: 0.0513 AC: 385 AN: 7512

Other (OTH) AF: 0.0730 AC: 40 AN: 548

GnomAD4 genome AF: 0.0908 AC: 13811 AN: 152112 Hom.: 826 Cov.: 32 AF XY: 0.0900 AC XY: 6693 AN XY: 74376

African (AFR) AF: 0.158 AC: 6567 AN: 41484

American (AMR) AF: 0.103 AC: 1579 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3470

East Asian (EAS) AF: 0.142 AC: 733 AN: 5164

South Asian (SAS) AF: 0.132 AC: 636 AN: 4812

European-Finnish (FIN) AF: 0.0220 AC: 233 AN: 10606

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0544 AC: 3699 AN: 67974

Other (OTH) AF: 0.0863 AC: 182 AN: 2110

Alfa AF: 0.0594 Hom.: 191

Bravo AF: 0.0998

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.18
PhyloP100		-0.27
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: rs918; hg19: chr8-15967078;