8-16120616-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr8-16120616-T-TAAAAA
• rs60866666
• NM_138715.3:c.1034-15_1034-11dupTTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_138715.3(MSR1):​c.1034-15_1034-11dupTTTTT 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 0.037 (50 hom., cov: 0)
  • Exomes 𝑓: 0.0085 (14 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 14 Unknown gene

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.1034-15_1034-11dupTTTTT		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.1088-15_1088-11dupTTTTT		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.1034-10403_1034-10399dupTTTTT		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_1034-10insTTTTT		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.1088-11_1088-10insTTTTT		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.1034-10399_1034-10398insTTTTT		intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 2338 AN: 63404 Hom.: 50 Cov.: 0

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.0122

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.0280

Gnomad SAS AF: 0.00465

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0172

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0345

GnomAD4 exome AF: 0.00853 AC: 9597 AN: 1125202 Hom.: 14 Cov.: 0 AF XY: 0.00844 AC XY: 4700 AN XY: 557044

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

African (AFR) AF: 0.0101 AC: 225 AN: 22258

American (AMR) AF: 0.0152 AC: 336 AN: 22164

Ashkenazi Jewish (ASJ) AF: 0.00792 AC: 154 AN: 19454

East Asian (EAS) AF: 0.00934 AC: 258 AN: 27620

South Asian (SAS) AF: 0.00381 AC: 230 AN: 60314

European-Finnish (FIN) AF: 0.00676 AC: 177 AN: 26176

Middle Eastern (MID) AF: 0.00527 AC: 16 AN: 3034

European-Non Finnish (NFE) AF: 0.00871 AC: 7824 AN: 898504

Other (OTH) AF: 0.00825 AC: 377 AN: 45678

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0368 AC: 2336 AN: 63406 Hom.: 50 Cov.: 0 AF XY: 0.0350 AC XY: 998 AN XY: 28518

African (AFR) AF: 0.0329 AC: 541 AN: 16440

American (AMR) AF: 0.0344 AC: 143 AN: 4156

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 94 AN: 1988

East Asian (EAS) AF: 0.0280 AC: 58 AN: 2068

South Asian (SAS) AF: 0.00470 AC: 7 AN: 1488

European-Finnish (FIN) AF: 0.0107 AC: 10 AN: 936

Middle Eastern (MID) AF: 0.0172 AC: 1 AN: 58

European-Non Finnish (NFE) AF: 0.0414 AC: 1450 AN: 35022

Other (OTH) AF: 0.0343 AC: 26 AN: 758

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs60866666; hg19: chr8-15978125;