chr8-16120616-TAAAAAAAAAAAAAAAA-T

Variant names:

• chr8-16120616-TAAAAAAAAAAAAAAAA-T
• rs60866666
• NM_138715.3:c.1034-26_1034-11delTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_138715.3(MSR1):​c.1034-26_1034-11delTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000793 in 1,134,572 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.1034-26_1034-11delTTTTTTTTTTTTTTTT		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.1088-26_1088-11delTTTTTTTTTTTTTTTT		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.1034-10414_1034-10399delTTTTTTTTTTTTTTTT		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.1034-26_1034-11delTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.1088-26_1088-11delTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.1034-10414_1034-10399delTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000793 AC: 9 AN: 1134572 Hom.: 0 AF XY: 0.00000890 AC XY: 5 AN XY: 561542

African (AFR) AF: 0.00 AC: 0 AN: 22446

American (AMR) AF: 0.00 AC: 0 AN: 22288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19566

East Asian (EAS) AF: 0.000324 AC: 9 AN: 27820

South Asian (SAS) AF: 0.00 AC: 0 AN: 60408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3052

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 906680

Other (OTH) AF: 0.00 AC: 0 AN: 46042

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

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;