16-28495811-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018690.4(APOBR):c.770G>T(p.Cys257Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000437 in 1,602,664 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

APOBR
NM_018690.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0950

Variant links:

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]

APOBR links:

CLN3 (HGNC:2074): (CLN3 lysosomal/endosomal transmembrane protein, battenin) This gene encodes a protein that is involved in lysosomal function. Mutations in this, as well as other neuronal ceroid-lipofuscinosis (CLN) genes, cause neurodegenerative diseases commonly known as Batten disease or collectively known as neuronal ceroid lipofuscinoses (NCLs). Many alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

CLN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0828557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBR	NM_018690.4 link	c.770G>T	p.Cys257Phe	missense_variant	Exon 2 of 4	ENST00000564831.6	NP_061160.3	Q0VD83-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOBR	ENST00000564831.6 link	c.770G>T	p.Cys257Phe	missense_variant	Exon 2 of 4	1	NM_018690.4	ENSP00000457539.1	Q0VD83-4
CLN3	ENST00000566040.1 link	n.-236C>A		upstream_gene_variant		4
CLN3	ENST00000636355.1 link	n.-244C>A		upstream_gene_variant		5
CLN3	ENST00000637686.1 link	n.-244C>A		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450508

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720408

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000474

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000642

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.770G>T (p.C257F) alteration is located in exon 2 (coding exon 2) of the APOBR gene. This alteration results from a G to T substitution at nucleotide position 770, causing the cysteine (C) at amino acid position 257 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0092

.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.083

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.038

Sift

Benign

0.057

T;T

Sift4G

Uncertain

0.053

T;T

Vest4

0.12

MutPred

0.23

Gain of catalytic residue at C257 (P = 0.0567);Gain of catalytic residue at C257 (P = 0.0567);

MVP

0.44

MPC

0.16

ClinPred

0.15

GERP RS

-1.4

Varity_R

0.091

gMVP

0.0084

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over