rs10094727

chr8-16560861-A-Gchr8-16560861-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007061175.1(LOC101929028):n.873-48951T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,188 control chromosomes in the GnomAD database, including 48,002 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 0.77 (48002 hom., cov: 32)
• Consequence: LOC101929028 XR_007061175.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.924

Genes affected

LOC101929028 (HGNC:):

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC101929028	XR_007061175.1	n.873-48951T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSR1	ENST00000518026.5	c.-244+6389T>C		intron_variant		4
MSR1	ENST00000518343.5	n.29+6531T>C		intron_variant, non_coding_transcript_variant		4
MSR1	ENST00000522130.1	n.152+4674T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117594 AN: 152068 Hom.: 47981 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.806

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.773 AC: 117655 AN: 152188 Hom.: 48002 Cov.: 32 AF XY: 0.773 AC XY: 57541 AN XY: 74422

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.809

Alfa AF: 0.850 Hom.: 27357

Bravo AF: 0.744

Asia WGS AF: 0.699 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.5
Dann	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10094727; hg19: chr8-16418370;