8-16120615-TTAAAAA-T

Position:

• chr8-16120615-TTAAAAA-T

Variant summary

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

The NM_138715.3(MSR1):​c.1034-15_1034-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00474 in 1,325,632 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (4 hom., cov: 0)
  • Exomes 𝑓: 0.0041 (12 hom.)
• Consequence: MSR1 NM_138715.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.86

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 8-16120615-TTAAAAA-T is Benign according to our data. Variant chr8-16120615-TTAAAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 782854.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSR1	NM_138715.3	c.1034-15_1034-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000262101.10
MSR1	NM_001363744.1	c.1088-15_1088-10del		splice_polypyrimidine_tract_variant, intron_variant
MSR1	NM_138716.3	c.1034-10403_1034-10398del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSR1	ENST00000262101.10	c.1034-15_1034-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_138715.3	P1
MSR1	ENST00000355282.6	c.1034-10403_1034-10398del		intron_variant		1
MSR1	ENST00000445506.6	c.1088-15_1088-10del		splice_polypyrimidine_tract_variant, intron_variant		1
MSR1	ENST00000350896.3	c.1034-10403_1034-10398del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 1059 AN: 43276 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.00164

Gnomad EAS AF: 0.00205

Gnomad SAS AF: 0.00649

Gnomad FIN AF: 0.000805

Gnomad MID AF: 0.0303

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0361

GnomAD4 exome AF: 0.00408 AC: 5231 AN: 1282352 Hom.: 12 AF XY: 0.00409 AC XY: 2584 AN XY: 631078

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.0200

Gnomad4 ASJ exome AF: 0.000547

Gnomad4 EAS exome AF: 0.0258

Gnomad4 SAS exome AF: 0.0118

Gnomad4 FIN exome AF: 0.000792

Gnomad4 NFE exome AF: 0.00256

Gnomad4 OTH exome AF: 0.00490

GnomAD4 genome AF: 0.0244 AC: 1057 AN: 43280 Hom.: 4 Cov.: 0 AF XY: 0.0254 AC XY: 514 AN XY: 20240

Gnomad4 AFR AF: 0.0554

Gnomad4 AMR AF: 0.0282

Gnomad4 ASJ AF: 0.00164

Gnomad4 EAS AF: 0.00206

Gnomad4 SAS AF: 0.00604

Gnomad4 FIN AF: 0.000805

Gnomad4 NFE AF: 0.0162

Gnomad4 OTH AF: 0.0357

Alfa AF: 0.00868 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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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: rs758932057; hg19: chr8-15978124;