rs40831

chr16-28497126-A-Gchr16-28497126-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018690.4(APOBR):c.2085A>G(p.Ala695=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOBR	NM_018690.4	c.2085A>G	p.Ala695=	synonymous_variant	2/4	ENST00000564831.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOBR	ENST00000564831.6	c.2085A>G	p.Ala695=	synonymous_variant	2/4	1	NM_018690.4	P1

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

GnomAD3 exomes AF: 0.457 AC: 105580 AN: 230918 Hom.: 24812 AF XY: 0.457 AC XY: 57241 AN XY: 125146

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 SAS exome AF: 0.572

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

Gnomad4 AFR exome AF: 0.514

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.429

Gnomad4 OTH exome AF: 0.424

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

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.402

Alfa AF: 0.412 Hom.: 14108

Bravo AF: 0.456

Asia WGS AF: 0.508 AC: 1760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.8
Dann	Benign	0.29

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