NM_018690.4:c.1282C>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018690.4(APOBR):​c.1282C>A​(p.Pro428Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: APOBR NM_018690.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03061676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBR	NM_018690.4	c.1282C>A	p.Pro428Thr	missense_variant	Exon 2 of 4	ENST00000564831.6	NP_061160.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBR	ENST00000564831.6	c.1282C>A	p.Pro428Thr	missense_variant	Exon 2 of 4	1	NM_018690.4	ENSP00000457539.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430892 Hom.: 0 Cov.: 72 AF XY: 0.00 AC XY: 0 AN XY: 709220

African (AFR) AF: 0.00 AC: 0 AN: 32466

American (AMR) AF: 0.00 AC: 0 AN: 39836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23672

East Asian (EAS) AF: 0.00 AC: 0 AN: 39402

South Asian (SAS) AF: 0.00 AC: 0 AN: 81694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096984

Other (OTH) AF: 0.00 AC: 0 AN: 58920

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.033
DANN	Benign	0.80
DEOGEN2	Benign	0.0018	.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.18	T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.031	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	.;N
PhyloP100		-0.56
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.057
Sift	Benign	0.72	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.029
MutPred		0.12		.;Loss of loop (P = 0.0153);
MVP		0.33
MPC		0.053
ClinPred		0.033	T
GERP RS		0.49
Varity_R		0.027
gMVP		0.019

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;