chr8-16155201-G-T

Position:

• chr8-16155201-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSR1	NM_138715.3	c.818-57C>A		intron_variant		ENST00000262101.10	NP_619729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10	c.818-57C>A		intron_variant		1	NM_138715.3	ENSP00000262101.5

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

Gnomad4 AFR exome AF: 0.00655

Gnomad4 AMR exome AF: 0.0217

Gnomad4 ASJ exome AF: 0.0837

Gnomad4 EAS exome AF: 0.00820

Gnomad4 SAS exome AF: 0.0793

Gnomad4 FIN exome AF: 0.0213

Gnomad4 NFE exome AF: 0.0379

Gnomad4 OTH exome AF: 0.0424

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

Gnomad4 AFR AF: 0.00672

Gnomad4 AMR AF: 0.0344

Gnomad4 ASJ AF: 0.0750

Gnomad4 EAS AF: 0.0138

Gnomad4 SAS AF: 0.0808

Gnomad4 FIN AF: 0.0209

Gnomad4 NFE AF: 0.0398

Gnomad4 OTH AF: 0.0437

Alfa AF: 0.0309 Hom.: 16

Bravo AF: 0.0298

Asia WGS AF: 0.0550 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs33959637; hg19: chr8-16012710;