rs673548

Positions:

• chr2-21014672-G-A
• chr2-21014672-G-T

Variant summary

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

The NM_000384.3(APOB):​c.3697-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,430,782 control chromosomes in the GnomAD database, including 53,513 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 0.25 (5628 hom., cov: 33)
  • Exomes 𝑓: 0.25 (47885 hom.)
• Consequence: APOB NM_000384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678

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=-0.82).
• BP6: Variant 2-21014672-G-A is Benign according to our data. Variant chr2-21014672-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOB	NM_000384.3	c.3697-79C>T		intron_variant		ENST00000233242.5	NP_000375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOB	ENST00000233242.5	c.3697-79C>T		intron_variant		1	NM_000384.3	ENSP00000233242	P1
APOB	ENST00000673739.2	c.*3003-79C>T		intron_variant, NMD_transcript_variant				ENSP00000501110
APOB	ENST00000673882.2	c.*2792-79C>T		intron_variant, NMD_transcript_variant				ENSP00000501253

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37936 AN: 151978 Hom.: 5628 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.247 AC: 315505 AN: 1278686 Hom.: 47885 AF XY: 0.254 AC XY: 163961 AN XY: 644286

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.726

Gnomad4 SAS exome AF: 0.496

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.249 AC: 37944 AN: 152096 Hom.: 5628 Cov.: 33 AF XY: 0.258 AC XY: 19161 AN XY: 74332

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.246

Alfa AF: 0.234 Hom.: 9965

Bravo AF: 0.244

Asia WGS AF: 0.600 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.86
DANN	Benign	0.67

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: rs673548; hg19: chr2-21237544;