chr16-28497126-A-G

Variant names:

• chr16-28497126-A-G
• rs40831
• NM_018690.4:c.2085A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018690.4(APOBR):​c.2085A>G​(p.Ala695Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,603,570 control chromosomes in the GnomAD database, including 158,570 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 0.46 (16698 hom., cov: 32)
  • Exomes 𝑓: 0.44 (141872 hom.)
• Consequence: APOBR NM_018690.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• Publications: 35 publications found

Genes affected

APOBR (HGNC:24087): (apolipoprotein B receptor) Apolipoprotein B48 receptor is a macrophage receptor that binds to the apolipoprotein B48 of dietary triglyceride (TG)-rich lipoproteins. This receptor may provide essential lipids, lipid-soluble vitamins and other nutrients to reticuloendothelial cells. If overwhelmed with elevated plasma triglyceride, the apolipoprotein B48 receptor may contribute to foam cell formation, endothelial dysfunction, and atherothrombogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.756 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018690.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBR	NM_018690.4	MANE Select	c.2085A>G	p.Ala695Ala	synonymous	Exon 2 of 4	NP_061160.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBR	ENST00000564831.6	TSL:1 MANE Select	c.2085A>G	p.Ala695Ala	synonymous	Exon 2 of 4	ENSP00000457539.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70256 AN: 151894 Hom.: 16677 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.457 AC: 105580 AN: 230918 AF XY: 0.457

Gnomad AFR exome AF: 0.528

Gnomad AMR exome AF: 0.515

Gnomad ASJ exome AF: 0.329

Gnomad EAS exome AF: 0.338

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.423

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.438 AC: 636192 AN: 1451558 Hom.: 141872 Cov.: 85 AF XY: 0.442 AC XY: 318382 AN XY: 721074

African (AFR) AF: 0.514 AC: 17156 AN: 33348

American (AMR) AF: 0.523 AC: 22368 AN: 42784

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8403 AN: 25904

East Asian (EAS) AF: 0.304 AC: 11965 AN: 39372

South Asian (SAS) AF: 0.569 AC: 48174 AN: 84602

European-Finnish (FIN) AF: 0.507 AC: 26513 AN: 52318

Middle Eastern (MID) AF: 0.264 AC: 1523 AN: 5760

European-Non Finnish (NFE) AF: 0.429 AC: 474641 AN: 1107414

Other (OTH) AF: 0.424 AC: 25449 AN: 60056

GnomAD4 genome AF: 0.463 AC: 70328 AN: 152012 Hom.: 16698 Cov.: 32 AF XY: 0.467 AC XY: 34717 AN XY: 74308

African (AFR) AF: 0.526 AC: 21798 AN: 41462

American (AMR) AF: 0.462 AC: 7067 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3468

East Asian (EAS) AF: 0.350 AC: 1798 AN: 5136

South Asian (SAS) AF: 0.582 AC: 2805 AN: 4822

European-Finnish (FIN) AF: 0.512 AC: 5416 AN: 10574

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29208 AN: 67944

Other (OTH) AF: 0.402 AC: 847 AN: 2108

Alfa AF: 0.416 Hom.: 17180

Bravo AF: 0.456

Asia WGS AF: 0.508 AC: 1760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.29
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs40831; hg19: chr16-28508447; COSMIC: COSV60488608; COSMIC: COSV60488608;