rs34175190

Variant names:

• chr8-16120602-T-A
• rs34175190
• NM_138715.3:c.1038A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-16120602-T-A
• chr8-16120602-T-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_138715.3(MSR1):​c.1038A>T​(p.Pro346Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P346P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSR1 NM_138715.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• Publications: 5 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.989 with no splicing effect.

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.1038A>T	p.Pro346Pro	synonymous	Exon 9 of 10	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.1092A>T	p.Pro364Pro	synonymous	Exon 9 of 10	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.1034-10384A>T		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.1038A>T	p.Pro346Pro	synonymous	Exon 9 of 10	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.1092A>T	p.Pro364Pro	synonymous	Exon 9 of 10	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.1034-10384A>T		intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 99102 Hom.: 0 Cov.: 21

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

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1450750 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 721682

African (AFR) AF: 0.00 AC: 0 AN: 32694

American (AMR) AF: 0.00 AC: 0 AN: 42898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25816

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.00 AC: 0 AN: 84424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5406

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108906

Other (OTH) AF: 0.00 AC: 0 AN: 59884

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 99102 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 44732

African (AFR) AF: 0.00 AC: 0 AN: 23650

American (AMR) AF: 0.00 AC: 0 AN: 6616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2926

East Asian (EAS) AF: 0.00 AC: 0 AN: 3580

South Asian (SAS) AF: 0.00 AC: 0 AN: 3228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 92

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 54292

Other (OTH) AF: 0.00 AC: 0 AN: 1226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.63
PhyloP100		-0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34175190; hg19: chr8-15978111;