8-16143708-T-TATA

Position:

• chr8-16143708-T-TATA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_138715.3(MSR1):​c.980-98_980-97insTAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 828,288 control chromosomes in the GnomAD database, including 9,870 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (2543 hom., cov: 30)
  • Exomes 𝑓: 0.10 (7327 hom.)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSR1	NM_138715.3	c.980-98_980-97insTAT		intron_variant		ENST00000262101.10	NP_619729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10	c.980-98_980-97insTAT		intron_variant		1	NM_138715.3	ENSP00000262101.5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21558 AN: 151840 Hom.: 2530 Cov.: 30

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.101 AC: 68213 AN: 676330 Hom.: 7327 AF XY: 0.102 AC XY: 36985 AN XY: 361144

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.0582

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.0258

Gnomad4 NFE exome AF: 0.0523

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.142 AC: 21612 AN: 151958 Hom.: 2543 Cov.: 30 AF XY: 0.145 AC XY: 10744 AN XY: 74294

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0284

Gnomad4 NFE AF: 0.0529

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0981 Hom.: 165

Bravo AF: 0.161

Asia WGS AF: 0.282 AC: 976 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3036811; hg19: chr8-16001217;