8-16155201-G-T

Variant names:

• chr8-16155201-G-T
• rs33959637
• NM_138715.3:c.818-57C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138715.3(MSR1):​c.818-57C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,299,366 control chromosomes in the GnomAD database, including 1,266 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (102 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1164 hom.)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0742 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.818-57C>A		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.872-57C>A		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.818-57C>A		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.818-57C>A		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.872-57C>A		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.818-57C>A		intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 4576 AN: 151880 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.00674

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0345

Gnomad ASJ AF: 0.0750

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.0801

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.0441

GnomAD4 exome AF: 0.0390 AC: 44752 AN: 1147368 Hom.: 1164 AF XY: 0.0410 AC XY: 23940 AN XY: 583658

African (AFR) AF: 0.00655 AC: 179 AN: 27338

American (AMR) AF: 0.0217 AC: 907 AN: 41856

Ashkenazi Jewish (ASJ) AF: 0.0837 AC: 1980 AN: 23654

East Asian (EAS) AF: 0.00820 AC: 307 AN: 37420

South Asian (SAS) AF: 0.0793 AC: 6175 AN: 77912

European-Finnish (FIN) AF: 0.0213 AC: 1085 AN: 50924

Middle Eastern (MID) AF: 0.0822 AC: 416 AN: 5060

European-Non Finnish (NFE) AF: 0.0379 AC: 31606 AN: 833704

Other (OTH) AF: 0.0424 AC: 2097 AN: 49500

GnomAD4 genome AF: 0.0301 AC: 4579 AN: 151998 Hom.: 102 Cov.: 32 AF XY: 0.0302 AC XY: 2243 AN XY: 74286

African (AFR) AF: 0.00672 AC: 279 AN: 41526

American (AMR) AF: 0.0344 AC: 524 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.0750 AC: 260 AN: 3466

East Asian (EAS) AF: 0.0138 AC: 71 AN: 5158

South Asian (SAS) AF: 0.0808 AC: 389 AN: 4814

European-Finnish (FIN) AF: 0.0209 AC: 222 AN: 10608

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0398 AC: 2702 AN: 67900

Other (OTH) AF: 0.0437 AC: 92 AN: 2106

Alfa AF: 0.0373 Hom.: 184

Bravo AF: 0.0298

Asia WGS AF: 0.0550 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.43
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs33959637; hg19: chr8-16012710;