chr8-16120616-T-TAAAA

Variant names:

• chr8-16120616-T-TAAAA
• rs60866666
• NM_138715.3:c.1034-14_1034-11dupTTTT

Variant summary

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

The NM_138715.3(MSR1):​c.1034-14_1034-11dupTTTT 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 0.029 (45 hom., cov: 0)
  • Exomes 𝑓: 0.011 (2 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 2 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.1034-14_1034-11dupTTTT		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.1088-14_1088-11dupTTTT		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.1034-10402_1034-10399dupTTTT		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_1034-10insTTTT		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.1088-11_1088-10insTTTT		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.1034-10399_1034-10398insTTTT		intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 1856 AN: 63410 Hom.: 45 Cov.: 0

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.00610

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.0272

Gnomad EAS AF: 0.0953

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.0172

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0406

GnomAD4 exome AF: 0.0108 AC: 12082 AN: 1120268 Hom.: 2 Cov.: 0 AF XY: 0.0106 AC XY: 5880 AN XY: 554792

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

African (AFR) AF: 0.0169 AC: 372 AN: 22026

American (AMR) AF: 0.0202 AC: 445 AN: 22048

Ashkenazi Jewish (ASJ) AF: 0.00990 AC: 192 AN: 19400

East Asian (EAS) AF: 0.0210 AC: 572 AN: 27266

South Asian (SAS) AF: 0.00445 AC: 268 AN: 60210

European-Finnish (FIN) AF: 0.00942 AC: 246 AN: 26120

Middle Eastern (MID) AF: 0.00628 AC: 19 AN: 3024

European-Non Finnish (NFE) AF: 0.0105 AC: 9435 AN: 894716

Other (OTH) AF: 0.0117 AC: 533 AN: 45458

⚠️ 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: 0.0293 AC: 1855 AN: 63410 Hom.: 45 Cov.: 0 AF XY: 0.0304 AC XY: 866 AN XY: 28498

African (AFR) AF: 0.0386 AC: 635 AN: 16452

American (AMR) AF: 0.0488 AC: 202 AN: 4138

Ashkenazi Jewish (ASJ) AF: 0.0272 AC: 54 AN: 1986

East Asian (EAS) AF: 0.0954 AC: 197 AN: 2064

South Asian (SAS) AF: 0.0162 AC: 24 AN: 1484

European-Finnish (FIN) AF: 0.0150 AC: 14 AN: 936

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

European-Non Finnish (NFE) AF: 0.0198 AC: 694 AN: 35032

Other (OTH) AF: 0.0404 AC: 31 AN: 768

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;