NM_138715.3:c.1034-17_1034-10delTTTTTTTA

Variant names:

• chr8-16120615-TTAAAAAAA-T
• rs751806093
• NM_138715.3:c.1034-17_1034-10delTTTTTTTA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_138715.3(MSR1):​c.1034-17_1034-10delTTTTTTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000757 in 1,288,754 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00076 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• 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: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 8-16120615-TTAAAAAAA-T is Benign according to our data. Variant chr8-16120615-TTAAAAAAA-T is described in ClinVar as Benign. ClinVar VariationId is 3042130.Status of the report is no_assertion_criteria_provided, 0 stars.

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_1034-10delTTTTTTTA		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.1088-17_1088-10delTTTTTTTA		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.1034-10405_1034-10398delTTTTTTTA		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_1034-10delTTTTTTTA		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.1088-17_1088-10delTTTTTTTA		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.1034-10405_1034-10398delTTTTTTTA		intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 43306 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00664 AC: 304 AN: 45782 AF XY: 0.00561

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.0242

Gnomad ASJ exome AF: 0.000279

Gnomad EAS exome AF: 0.0260

Gnomad FIN exome AF: 0.000374

Gnomad NFE exome AF: 0.00324

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.000757 AC: 976 AN: 1288754 Hom.: 0 AF XY: 0.000797 AC XY: 506 AN XY: 634720

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

African (AFR) AF: 0.00189 AC: 48 AN: 25418

American (AMR) AF: 0.00710 AC: 157 AN: 22098

Ashkenazi Jewish (ASJ) AF: 0.0000911 AC: 2 AN: 21942

East Asian (EAS) AF: 0.00461 AC: 148 AN: 32094

South Asian (SAS) AF: 0.00251 AC: 164 AN: 65260

European-Finnish (FIN) AF: 0.000264 AC: 8 AN: 30350

Middle Eastern (MID) AF: 0.00252 AC: 9 AN: 3566

European-Non Finnish (NFE) AF: 0.000370 AC: 383 AN: 1035468

Other (OTH) AF: 0.00108 AC: 57 AN: 52558

⚠️ 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: AC0 AF: 0.00 AC: 0 AN: 43306 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20254

African (AFR) AF: 0.00 AC: 0 AN: 9928

American (AMR) AF: 0.00 AC: 0 AN: 3686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1220

East Asian (EAS) AF: 0.00 AC: 0 AN: 1950

South Asian (SAS) AF: 0.00 AC: 0 AN: 2004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 66

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 22386

Other (OTH) AF: 0.00 AC: 0 AN: 554

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MSR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs751806093; hg19: chr8-15978124;