8-16120616-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_138715.3(MSR1):​c.1034-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (2690 hom., cov: 0)
  • Exomes 𝑓: 0.14 (58 hom.)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 8-16120616-TA-T is Benign according to our data. Variant chr8-16120616-TA-T is described in ClinVar as Benign. ClinVar VariationId is 2776135.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 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.1034-11delT		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.1088-11delT		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.1034-10399delT		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.1034-11delT		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.1088-11delT		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.1034-10399delT		intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes AF: 0.330 AC: 20803 AN: 63090 Hom.: 2689 Cov.: 0

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.139 AC: 151169 AN: 1084832 Hom.: 58 Cov.: 0 AF XY: 0.138 AC XY: 74006 AN XY: 536008

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

African (AFR) AF: 0.0529 AC: 1151 AN: 21750

American (AMR) AF: 0.0957 AC: 1983 AN: 20722

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 2266 AN: 18580

East Asian (EAS) AF: 0.112 AC: 2885 AN: 25826

South Asian (SAS) AF: 0.109 AC: 6070 AN: 55640

European-Finnish (FIN) AF: 0.110 AC: 2729 AN: 24820

Middle Eastern (MID) AF: 0.138 AC: 402 AN: 2906

European-Non Finnish (NFE) AF: 0.147 AC: 127906 AN: 870726

Other (OTH) AF: 0.132 AC: 5777 AN: 43862

⚠️ 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: 0.330 AC: 20803 AN: 63094 Hom.: 2690 Cov.: 0 AF XY: 0.325 AC XY: 9230 AN XY: 28402

African (AFR) AF: 0.128 AC: 2095 AN: 16392

American (AMR) AF: 0.335 AC: 1380 AN: 4120

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 871 AN: 1974

East Asian (EAS) AF: 0.365 AC: 757 AN: 2074

South Asian (SAS) AF: 0.363 AC: 542 AN: 1494

European-Finnish (FIN) AF: 0.292 AC: 272 AN: 930

Middle Eastern (MID) AF: 0.362 AC: 21 AN: 58

European-Non Finnish (NFE) AF: 0.412 AC: 14344 AN: 34802

Other (OTH) AF: 0.360 AC: 274 AN: 762

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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)		0.0		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;