chr8-16120616-TAAAAAAA-T

Variant names:

• chr8-16120616-TAAAAAAA-T
• rs60866666
• NM_138715.3:c.1034-17_1034-11delTTTTTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_138715.3(MSR1):​c.1034-17_1034-11delTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,195,444 control chromosomes in the GnomAD database, including 38 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.028 (33 hom., cov: 0)
  • Exomes 𝑓: 0.014 (5 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0285 (1811/63594) while in subpopulation NFE AF = 0.0318 (1117/35118). AF 95% confidence interval is 0.0303. There are 33 homozygotes in GnomAd4. There are 785 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 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.1034-17_1034-11delTTTTTTT		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.1088-17_1088-11delTTTTTTT		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.1034-10405_1034-10399delTTTTTTT		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.1034-17_1034-11delTTTTTTT		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.1088-17_1088-11delTTTTTTT		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.1034-10405_1034-10399delTTTTTTT		intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 1812 AN: 63592 Hom.: 32 Cov.: 0

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.000959

Gnomad SAS AF: 0.00796

Gnomad FIN AF: 0.0459

Gnomad MID AF: 0.0172

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0368

GnomAD4 exome AF: 0.0141 AC: 15931 AN: 1131850 Hom.: 5 AF XY: 0.0138 AC XY: 7715 AN XY: 560086

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

African (AFR) AF: 0.0146 AC: 327 AN: 22372

American (AMR) AF: 0.00616 AC: 137 AN: 22234

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 275 AN: 19480

East Asian (EAS) AF: 0.000540 AC: 15 AN: 27784

South Asian (SAS) AF: 0.00345 AC: 208 AN: 60318

European-Finnish (FIN) AF: 0.0148 AC: 386 AN: 26162

Middle Eastern (MID) AF: 0.00953 AC: 29 AN: 3044

European-Non Finnish (NFE) AF: 0.0155 AC: 13993 AN: 904542

Other (OTH) AF: 0.0122 AC: 561 AN: 45914

⚠️ 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: 0.0285 AC: 1811 AN: 63594 Hom.: 33 Cov.: 0 AF XY: 0.0275 AC XY: 785 AN XY: 28596

African (AFR) AF: 0.0279 AC: 460 AN: 16490

American (AMR) AF: 0.0214 AC: 89 AN: 4168

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 46 AN: 1992

East Asian (EAS) AF: 0.000961 AC: 2 AN: 2082

South Asian (SAS) AF: 0.00804 AC: 12 AN: 1492

European-Finnish (FIN) AF: 0.0459 AC: 43 AN: 936

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

European-Non Finnish (NFE) AF: 0.0318 AC: 1117 AN: 35118

Other (OTH) AF: 0.0366 AC: 28 AN: 764

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
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;