16-28496323-C-G

Variant names:

• chr16-28496323-C-G
• rs180743
• NM_018690.4:c.1282C>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 53 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 -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.

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.1282C>G	p.Pro428Ala	missense	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.1282C>G	p.Pro428Ala	missense	Exon 2 of 4	ENSP00000457539.1

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

GnomAD2 exomes AF: 0.362 AC: 80503 AN: 222404 AF XY: 0.355

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 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

African (AFR) AF: 0.394 AC: 12796 AN: 32464

American (AMR) AF: 0.413 AC: 16444 AN: 39780

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 6731 AN: 23654

East Asian (EAS) AF: 0.107 AC: 4227 AN: 39398

South Asian (SAS) AF: 0.232 AC: 18952 AN: 81640

European-Finnish (FIN) AF: 0.477 AC: 24940 AN: 52336

Middle Eastern (MID) AF: 0.213 AC: 1185 AN: 5568

European-Non Finnish (NFE) AF: 0.409 AC: 448675 AN: 1096844

Other (OTH) AF: 0.360 AC: 21212 AN: 58908

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

African (AFR) AF: 0.406 AC: 16810 AN: 41422

American (AMR) AF: 0.384 AC: 5874 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3464

East Asian (EAS) AF: 0.0967 AC: 496 AN: 5130

South Asian (SAS) AF: 0.220 AC: 1059 AN: 4818

European-Finnish (FIN) AF: 0.482 AC: 5087 AN: 10544

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.409 AC: 27809 AN: 67936

Other (OTH) AF: 0.346 AC: 730 AN: 2112

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 v4.9

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
MetaRNN	Benign	0.00032	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.56
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.016
Sift	Benign	1.0	T
Sift4G	Benign	0.89	T
Vest4		0.028
MPC		0.048
ClinPred		0.0027	T
GERP RS		0.49
Varity_R		0.017
gMVP		0.014
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs180743; hg19: chr16-28507644; COSMIC: COSV60489440; COSMIC: COSV60489440;