rs72552387

Variant names:

• chr8-16168568-C-A
• rs72552387
• NM_138715.3:c.520G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-16168568-C-A
• chr8-16168568-C-G
• chr8-16168568-C-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BS1_Supporting BS2

The NM_138715.3(MSR1):​c.520G>T​(p.Asp174Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,614,122 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (10 hom., cov: 33)
  • Exomes 𝑓: 0.00069 (16 hom.)
• Consequence: MSR1 NM_138715.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 1.11
• Publications: 21 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07389018).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00623 (949/152300) while in subpopulation AFR AF = 0.0216 (896/41566). AF 95% confidence interval is 0.0204. There are 10 homozygotes in GnomAd4. There are 467 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 10 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.520G>T	p.Asp174Tyr	missense	Exon 4 of 10	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.574G>T	p.Asp192Tyr	missense	Exon 4 of 10	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.520G>T	p.Asp174Tyr	missense	Exon 4 of 9	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.520G>T	p.Asp174Tyr	missense	Exon 4 of 10	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.574G>T	p.Asp192Tyr	missense	Exon 4 of 10	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.520G>T	p.Asp174Tyr	missense	Exon 3 of 8	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes AF: 0.00623 AC: 948 AN: 152182 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00165 AC: 414 AN: 251352 AF XY: 0.00132

Gnomad AFR exome AF: 0.0220

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000692 AC: 1011 AN: 1461822 Hom.: 16 Cov.: 32 AF XY: 0.000638 AC XY: 464 AN XY: 727202

African (AFR) AF: 0.0225 AC: 754 AN: 33480

American (AMR) AF: 0.000917 AC: 41 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5766

European-Non Finnish (NFE) AF: 0.0000683 AC: 76 AN: 1111968

Other (OTH) AF: 0.00195 AC: 118 AN: 60394

GnomAD4 genome AF: 0.00623 AC: 949 AN: 152300 Hom.: 10 Cov.: 33 AF XY: 0.00627 AC XY: 467 AN XY: 74450

African (AFR) AF: 0.0216 AC: 896 AN: 41566

American (AMR) AF: 0.00229 AC: 35 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68032

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00229 Hom.: 6

Bravo AF: 0.00673

ESP6500AA AF: 0.0175 AC: 77

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00197 AC: 239

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Prostate cancer (2)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.074	T
MetaSVM	Uncertain	0.0096	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.1
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.68
MVP		0.87
MPC		0.010
ClinPred		0.028	T
GERP RS		3.4
Varity_R		0.16
gMVP		0.32
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs72552387; hg19: chr8-16026077; COSMIC: COSV50508400; COSMIC: COSV50508400;