NM_000384.3:c.3121+359T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000384.3(APOB):​c.3121+359T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 151,990 control chromosomes in the GnomAD database, including 1,546 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1546 hom., cov: 32)

Consequence

APOB
NM_000384.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.242

Publications

26 publications found
Variant links:
Genes affected
APOB (HGNC:603): (apolipoprotein B) This gene product is the main apolipoprotein of chylomicrons and low density lipoproteins (LDL), and is the ligand for the LDL receptor. It occurs in plasma as two main isoforms, apoB-48 and apoB-100: the former is synthesized exclusively in the gut and the latter in the liver. The intestinal and the hepatic forms of apoB are encoded by a single gene from a single, very long mRNA. The two isoforms share a common N-terminal sequence. The shorter apoB-48 protein is produced after RNA editing of the apoB-100 transcript at residue 2180 (CAA->UAA), resulting in the creation of a stop codon, and early translation termination. Mutations in this gene or its regulatory region cause hypobetalipoproteinemia, normotriglyceridemic hypobetalipoproteinemia, and hypercholesterolemia due to ligand-defective apoB, diseases affecting plasma cholesterol and apoB levels. [provided by RefSeq, Dec 2019]
APOB Gene-Disease associations (from GenCC):
  • hypercholesterolemia, autosomal dominant, type B
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
  • familial hypobetalipoproteinemia 1
    Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
  • homozygous familial hypercholesterolemia
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APOBNM_000384.3 linkc.3121+359T>C intron_variant Intron 20 of 28 ENST00000233242.5 NP_000375.3 P04114Q7Z7Q0Q59HB3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APOBENST00000233242.5 linkc.3121+359T>C intron_variant Intron 20 of 28 1 NM_000384.3 ENSP00000233242.1 P04114
APOBENST00000673739.2 linkn.*2427+359T>C intron_variant Intron 19 of 24 ENSP00000501110.2 A0A669KB70
APOBENST00000673882.2 linkn.*2427+359T>C intron_variant Intron 19 of 22 ENSP00000501253.2 A0A669KB70

Frequencies

GnomAD3 genomes
AF:
0.135
AC:
20435
AN:
151872
Hom.:
1541
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.188
Gnomad AMI
AF:
0.109
Gnomad AMR
AF:
0.177
Gnomad ASJ
AF:
0.287
Gnomad EAS
AF:
0.0396
Gnomad SAS
AF:
0.113
Gnomad FIN
AF:
0.129
Gnomad MID
AF:
0.142
Gnomad NFE
AF:
0.0948
Gnomad OTH
AF:
0.139
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.135
AC:
20476
AN:
151990
Hom.:
1546
Cov.:
32
AF XY:
0.137
AC XY:
10206
AN XY:
74286
show subpopulations
African (AFR)
AF:
0.188
AC:
7785
AN:
41442
American (AMR)
AF:
0.177
AC:
2705
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
0.287
AC:
994
AN:
3468
East Asian (EAS)
AF:
0.0399
AC:
206
AN:
5164
South Asian (SAS)
AF:
0.113
AC:
544
AN:
4800
European-Finnish (FIN)
AF:
0.129
AC:
1366
AN:
10576
Middle Eastern (MID)
AF:
0.150
AC:
44
AN:
294
European-Non Finnish (NFE)
AF:
0.0948
AC:
6440
AN:
67958
Other (OTH)
AF:
0.139
AC:
293
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
925
1850
2774
3699
4624
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
216
432
648
864
1080
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.114
Hom.:
3057
Bravo
AF:
0.143
Asia WGS
AF:
0.0870
AC:
303
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
2.1
DANN
Benign
0.74
PhyloP100
-0.24
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12713956; hg19: chr2-21241505; API