8-16143708-T-TATA

Variant names:

• chr8-16143708-T-TATA
• rs3036811
• NM_138715.3:c.980-98_980-97insTAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_138715.3(MSR1):​c.980-98_980-97insTAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 828,288 control chromosomes in the GnomAD database, including 9,870 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (2543 hom., cov: 30)
  • Exomes 𝑓: 0.10 (7327 hom.)
• Consequence: MSR1 NM_138715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Barrett esophagus

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138715.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSR1	NM_138715.3	MANE Select	c.980-98_980-97insTAT		intron	N/A	NP_619729.1	P21757-1
	MSR1	NM_001363744.1		c.1034-98_1034-97insTAT		intron	N/A	NP_001350673.1	B4DDJ5
	MSR1	NM_138716.3		c.980-98_980-97insTAT		intron	N/A	NP_619730.1	P21757-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSR1	ENST00000262101.10	TSL:1 MANE Select	c.980-98_980-97insTAT		intron	N/A	ENSP00000262101.5	P21757-1
	MSR1	ENST00000445506.6	TSL:1	c.1034-98_1034-97insTAT		intron	N/A	ENSP00000405453.2	B4DDJ5
	MSR1	ENST00000355282.6	TSL:1	c.980-98_980-97insTAT		intron	N/A	ENSP00000347430.2	P21757-3

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21558 AN: 151840 Hom.: 2530 Cov.: 30

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.101 AC: 68213 AN: 676330 Hom.: 7327 AF XY: 0.102 AC XY: 36985 AN XY: 361144

African (AFR) AF: 0.270 AC: 4724 AN: 17492

American (AMR) AF: 0.223 AC: 8202 AN: 36794

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 1193 AN: 20504

East Asian (EAS) AF: 0.464 AC: 15322 AN: 33020

South Asian (SAS) AF: 0.177 AC: 11608 AN: 65642

European-Finnish (FIN) AF: 0.0258 AC: 982 AN: 38086

Middle Eastern (MID) AF: 0.0749 AC: 262 AN: 3496

European-Non Finnish (NFE) AF: 0.0523 AC: 22324 AN: 427166

Other (OTH) AF: 0.105 AC: 3596 AN: 34130

GnomAD4 genome AF: 0.142 AC: 21612 AN: 151958 Hom.: 2543 Cov.: 30 AF XY: 0.145 AC XY: 10744 AN XY: 74294

African (AFR) AF: 0.274 AC: 11325 AN: 41400

American (AMR) AF: 0.170 AC: 2594 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3472

East Asian (EAS) AF: 0.443 AC: 2266 AN: 5120

South Asian (SAS) AF: 0.204 AC: 983 AN: 4824

European-Finnish (FIN) AF: 0.0284 AC: 301 AN: 10606

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0529 AC: 3593 AN: 67978

Other (OTH) AF: 0.128 AC: 270 AN: 2110

Alfa AF: 0.0981 Hom.: 165

Bravo AF: 0.161

Asia WGS AF: 0.282 AC: 976 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.058
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3036811; hg19: chr8-16001217;