8-16120446-G-A

Position:

chr8-16120446-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_138715.3(MSR1):c.1194C>T(p.Ala398Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000521 in 1,613,528 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 29)

Exomes 𝑓: 0.00055 ( 18 hom. )

Consequence

MSR1
NM_138715.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41

Variant links:

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]

MSR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 8-16120446-G-A is Benign according to our data. Variant chr8-16120446-G-A is described in ClinVar as [Benign]. Clinvar id is 712059.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-16120446-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.41 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000264 (40/151688) while in subpopulation SAS AF= 0.00814 (39/4794). AF 95% confidence interval is 0.00612. There are 1 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSR1	NM_138715.3 link	c.1194C>T	p.Ala398Ala	synonymous_variant	9/10	ENST00000262101.10	NP_619729.1	P21757-1
MSR1	NM_001363744.1 link	c.1248C>T	p.Ala416Ala	synonymous_variant	9/10		NP_001350673.1
MSR1	NM_138716.3 link	c.1034-10228C>T		intron_variant			NP_619730.1	P21757-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MSR1	ENST00000262101.10 link	c.1194C>T	p.Ala398Ala	synonymous_variant	9/10	1	NM_138715.3	ENSP00000262101.5	P21757-1
MSR1	ENST00000445506.6 link	c.1248C>T	p.Ala416Ala	synonymous_variant	9/10	1		ENSP00000405453.2	B4DDJ5
MSR1	ENST00000355282.6 link	c.1034-10228C>T		intron_variant		1		ENSP00000347430.2	P21757-3
MSR1	ENST00000350896.3 link	c.1034-10228C>T		intron_variant		5		ENSP00000262100.3	P21757-3

Frequencies

GnomAD3 genomes

AF:

0.000264

AC:

AN:

151570

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00813

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00111

AC:

278

AN:

251450

Hom.:

AF XY:

0.00155

AC XY:

210

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00895

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000547

AC:

800

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000818

AC XY:

595

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00883

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000264

AC:

AN:

151688

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

AN XY:

74136

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00814

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.0000302

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.6

DANN

Benign

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over