8-16120616-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_138715.3(MSR1):c.1034-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (2690 hom., cov: 0)
  • Exomes 𝑓: 0.14 (58 hom.)
• Consequence: MSR1 NM_138715.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.140

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 -10 ACMG points.

• BP6: Variant 8-16120616-TA-T is Benign according to our data. Variant chr8-16120616-TA-T is described in ClinVar as [Benign]. Clinvar id is 2776135.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSR1	NM_138715.3	c.1034-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000262101.10
MSR1	NM_001363744.1	c.1088-11del		splice_polypyrimidine_tract_variant, intron_variant
MSR1	NM_138716.3	c.1034-10399del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSR1	ENST00000262101.10	c.1034-11del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_138715.3	P1
MSR1	ENST00000355282.6	c.1034-10399del		intron_variant		1
MSR1	ENST00000445506.6	c.1088-11del		splice_polypyrimidine_tract_variant, intron_variant		1
MSR1	ENST00000350896.3	c.1034-10399del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.330 AC: 20803 AN: 63090 Hom.: 2689 Cov.: 0

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.139 AC: 151169 AN: 1084832 Hom.: 58 Cov.: 0 AF XY: 0.138 AC XY: 74006 AN XY: 536008

Gnomad4 AFR exome AF: 0.0529

Gnomad4 AMR exome AF: 0.0957

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.330 AC: 20803 AN: 63094 Hom.: 2690 Cov.: 0 AF XY: 0.325 AC XY: 9230 AN XY: 28402

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.360

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs60866666; hg19: chr8-15978125;