rs12713956

Positions:

• chr2-21018633-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.13 (1546 hom., cov: 32)
• Consequence: APOB NM_000384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-21018633-A-G is Benign according to our data. Variant chr2-21018633-A-G is described in Lovd as [Likely_benign].
• 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/exons	MANE	Protein	UniProt
APOB	NM_000384.3	c.3121+359T>C		intron_variant		ENST00000233242.5	NP_000375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOB	ENST00000233242.5	c.3121+359T>C		intron_variant		1	NM_000384.3	ENSP00000233242.1
APOB	ENST00000673739.2	n.*2427+359T>C		intron_variant				ENSP00000501110.2
APOB	ENST00000673882.2	n.*2427+359T>C		intron_variant				ENSP00000501253.2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20435 AN: 151872 Hom.: 1541 Cov.: 32

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

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.0399

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.0948

Gnomad4 OTH AF: 0.139

Alfa AF: 0.111 Hom.: 877

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

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: rs12713956; hg19: chr2-21241505;