2-21040767-T-G

Position:

• chr2-21040767-T-G

Variant summary

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

The ENST00000233242.5(APOB):​c.383+171A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,244 control chromosomes in the GnomAD database, including 53,175 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 0.83 (53175 hom., cov: 34)
• Consequence: APOB ENST00000233242.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253

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=-0.78).
• BP6: Variant 2-21040767-T-G is Benign according to our data. Variant chr2-21040767-T-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOB	NM_000384.3	c.383+171A>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.383+171A>C		intron_variant		1	NM_000384.3	ENSP00000233242	P1
APOB	ENST00000399256.4	c.383+171A>C		intron_variant		1		ENSP00000382200
APOB	ENST00000673739.2	c.383+171A>C		intron_variant, NMD_transcript_variant				ENSP00000501110
APOB	ENST00000673882.2	c.383+171A>C		intron_variant, NMD_transcript_variant				ENSP00000501253

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126876 AN: 152126 Hom.: 53124 Cov.: 34

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.823

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.834 AC: 126982 AN: 152244 Hom.: 53175 Cov.: 34 AF XY: 0.835 AC XY: 62163 AN XY: 74426

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.825

Alfa AF: 0.843 Hom.: 6752

Bravo AF: 0.832

Asia WGS AF: 0.932 AC: 3242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.5
DANN	Benign	0.78

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: rs531819; hg19: chr2-21263639;