rs180743

Positions:

• chr16-28496323-C-G
• chr16-28496323-C-T

Variant summary

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

The NM_018690.4(APOBR):​c.1282C>G​(p.Pro428Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,582,498 control chromosomes in the GnomAD database, including 123,803 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.39 (12113 hom., cov: 32)
  • Exomes 𝑓: 0.39 (111690 hom.)
• Consequence: APOBR NM_018690.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.2421947E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOBR	NM_018690.4	c.1282C>G	p.Pro428Ala	missense_variant	2/4	ENST00000564831.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOBR	ENST00000564831.6	c.1282C>G	p.Pro428Ala	missense_variant	2/4	1	NM_018690.4	P1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59043 AN: 151788 Hom.: 12096 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0965

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.345

GnomAD3 exomes AF: 0.362 AC: 80503 AN: 222404 Hom.: 15903 AF XY: 0.355 AC XY: 42673 AN XY: 120060

Gnomad AFR exome AF: 0.410

Gnomad AMR exome AF: 0.403

Gnomad ASJ exome AF: 0.300

Gnomad EAS exome AF: 0.0873

Gnomad SAS exome AF: 0.231

Gnomad FIN exome AF: 0.482

Gnomad NFE exome AF: 0.403

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.388 AC: 555162 AN: 1430592 Hom.: 111690 Cov.: 72 AF XY: 0.384 AC XY: 272038 AN XY: 709036

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.389 AC: 59101 AN: 151906 Hom.: 12113 Cov.: 32 AF XY: 0.387 AC XY: 28764 AN XY: 74254

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.0967

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.346

Alfa AF: 0.326 Hom.: 1574

Bravo AF: 0.383

TwinsUK AF: 0.411 AC: 1523

ALSPAC AF: 0.408 AC: 1571

ESP6500AA AF: 0.409 AC: 1629

ESP6500EA AF: 0.390 AC: 3245

ExAC AF: 0.358 AC: 43213

Asia WGS AF: 0.225 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.28
DANN	Benign	0.84
DEOGEN2	Benign	0.0035	.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.15	T;T
MetaRNN	Benign	0.00032	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	.;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.10	N;N
REVEL	Benign	0.016
Sift	Benign	1.0	T;T
Sift4G	Benign	0.89	T;T
Vest4		0.028
MPC		0.048
ClinPred		0.0027	T
GERP RS		0.49
Varity_R		0.017
gMVP		0.014

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs180743; hg19: chr16-28507644; COSMIC: COSV60489440; COSMIC: COSV60489440;