16-28496323-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018690.4(APOBR):​c.1282C>T​(p.Pro428Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P428A) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05896929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBR	NM_018690.4	c.1282C>T	p.Pro428Ser	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>T	p.Pro428Ser	missense_variant	Exon 2 of 4	1	NM_018690.4	ENSP00000457539.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151840 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 72

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151840 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74156

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.43
DANN	Benign	0.97
DEOGEN2	Benign	0.0035	.;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.26	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	.;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.13	N;N
REVEL	Benign	0.0060
Sift	Benign	0.28	T;T
Sift4G	Benign	0.67	T;T
Vest4		0.024
MVP		0.39
MPC		0.050
ClinPred		0.048	T
GERP RS		0.49
Varity_R		0.021
gMVP		0.020

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: rs180743; hg19: chr16-28507644;