8-16109569-C-T

Position:

• chr8-16109569-C-T

Variant summary

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

The NM_138715.3(MSR1):​c.*516G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 165,536 control chromosomes in the GnomAD database, including 890 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 0.091 (826 hom., cov: 32)
  • Exomes 𝑓: 0.078 (64 hom.)
• Consequence: MSR1 NM_138715.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSR1	NM_138715.3	c.*516G>A		3_prime_UTR_variant	10/10	ENST00000262101.10	NP_619729.1
MSR1	NM_001363744.1	c.*516G>A		3_prime_UTR_variant	10/10		NP_001350673.1
MSR1	NM_138716.3	c.*516G>A		3_prime_UTR_variant	9/9		NP_619730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10	c.*516G>A		3_prime_UTR_variant	10/10	1	NM_138715.3	ENSP00000262101	P1
MSR1	ENST00000350896.3	c.*516G>A		3_prime_UTR_variant	9/9	5		ENSP00000262100

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13784 AN: 151992 Hom.: 824 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0544

Gnomad OTH AF: 0.0852

GnomAD4 exome AF: 0.0779 AC: 1046 AN: 13424 Hom.: 64 Cov.: 0 AF XY: 0.0763 AC XY: 548 AN XY: 7182

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.0154

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.0513

Gnomad4 OTH exome AF: 0.0730

GnomAD4 genome AF: 0.0908 AC: 13811 AN: 152112 Hom.: 826 Cov.: 32 AF XY: 0.0900 AC XY: 6693 AN XY: 74376

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0220

Gnomad4 NFE AF: 0.0544

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.0522 Hom.: 89

Bravo AF: 0.0998

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.18

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: rs918; hg19: chr8-15967078;