8-16120616-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAA

Variant names:

• chr8-16120616-T-TA
• rs60866666
• NM_138715.3:c.1034-11dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_138715.3(MSR1):​c.1034-11dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (120 hom., cov: 0)
  • Exomes 𝑓: 0.0082 (1 hom.)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 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.1034-11dupT		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.1088-11dupT		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.1034-10399dupT		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.1034-11_1034-10insT		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.1088-11_1088-10insT		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.1034-10399_1034-10398insT		intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 2431 AN: 63446 Hom.: 119 Cov.: 0

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.00201

Gnomad EAS AF: 0.00722

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0223

GnomAD4 exome AF: 0.00824 AC: 9277 AN: 1125776 Hom.: 1 Cov.: 0 AF XY: 0.00835 AC XY: 4653 AN XY: 556964

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0447 AC: 974 AN: 21780

American (AMR) AF: 0.0211 AC: 462 AN: 21888

Ashkenazi Jewish (ASJ) AF: 0.00674 AC: 131 AN: 19446

East Asian (EAS) AF: 0.0110 AC: 302 AN: 27512

South Asian (SAS) AF: 0.0157 AC: 931 AN: 59416

European-Finnish (FIN) AF: 0.0123 AC: 320 AN: 26018

Middle Eastern (MID) AF: 0.0109 AC: 33 AN: 3022

European-Non Finnish (NFE) AF: 0.00629 AC: 5665 AN: 901104

Other (OTH) AF: 0.0101 AC: 459 AN: 45590

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0383 AC: 2433 AN: 63448 Hom.: 120 Cov.: 0 AF XY: 0.0386 AC XY: 1102 AN XY: 28544

African (AFR) AF: 0.112 AC: 1848 AN: 16444

American (AMR) AF: 0.0272 AC: 113 AN: 4162

Ashkenazi Jewish (ASJ) AF: 0.00201 AC: 4 AN: 1986

East Asian (EAS) AF: 0.00723 AC: 15 AN: 2074

South Asian (SAS) AF: 0.0154 AC: 23 AN: 1490

European-Finnish (FIN) AF: 0.0161 AC: 15 AN: 934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 58

European-Non Finnish (NFE) AF: 0.0114 AC: 398 AN: 35042

Other (OTH) AF: 0.0222 AC: 17 AN: 766

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs60866666; hg19: chr8-15978125;