rs1904577

Variant names:

• chr8-16114175-G-A
• rs1904577
• NM_138715.3:c.1223-3957C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-16114175-G-A
• chr8-16114175-G-C

Variant summary

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

The NM_138715.3(MSR1):​c.1223-3957C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,672 control chromosomes in the GnomAD database, including 43,493 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 0.74 (43493 hom., cov: 29)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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 (NFE) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSR1	NM_138715.3	c.1223-3957C>T		intron_variant	Intron 9 of 9	ENST00000262101.10	NP_619729.1
MSR1	NM_001363744.1	c.1277-3957C>T		intron_variant	Intron 9 of 9		NP_001350673.1
MSR1	NM_138716.3	c.1034-3957C>T		intron_variant	Intron 8 of 8		NP_619730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSR1	ENST00000262101.10	c.1223-3957C>T		intron_variant	Intron 9 of 9	1	NM_138715.3	ENSP00000262101.5
MSR1	ENST00000445506.6	c.1277-3957C>T		intron_variant	Intron 9 of 9	1		ENSP00000405453.2
MSR1	ENST00000355282.6	c.1034-3957C>T		intron_variant	Intron 7 of 7	1		ENSP00000347430.2
MSR1	ENST00000350896.3	c.1034-3957C>T		intron_variant	Intron 8 of 8	5		ENSP00000262100.3

Frequencies

GnomAD3 genomes AF: 0.738 AC: 111783 AN: 151556 Hom.: 43480 Cov.: 29

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.737 AC: 111816 AN: 151672 Hom.: 43493 Cov.: 29 AF XY: 0.737 AC XY: 54648 AN XY: 74118

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.833

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.763

Alfa AF: 0.822 Hom.: 24967

Bravo AF: 0.714

Asia WGS AF: 0.754 AC: 2618 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.23

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: rs1904577; hg19: chr8-15971684;