NM_000384.3:c.693+410A>G

Variant names:

• chr2-21036690-T-C
• rs1469513
• NM_000384.3:c.693+410A>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.693+410A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,012 control chromosomes in the GnomAD database, including 9,600 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 0.34 (9600 hom., cov: 31)
• Consequence: APOB NM_000384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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 2-21036690-T-C is Benign according to our data. Variant chr2-21036690-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOB	NM_000384.3	c.693+410A>G		intron_variant	Intron 6 of 28	ENST00000233242.5	NP_000375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOB	ENST00000233242.5	c.693+410A>G		intron_variant	Intron 6 of 28	1	NM_000384.3	ENSP00000233242.1
APOB	ENST00000399256.4	c.693+410A>G		intron_variant	Intron 6 of 16	1		ENSP00000382200.4
APOB	ENST00000673739.2	n.539+410A>G		intron_variant	Intron 5 of 24			ENSP00000501110.2
APOB	ENST00000673882.2	n.539+410A>G		intron_variant	Intron 5 of 22			ENSP00000501253.2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51437 AN: 151894 Hom.: 9600 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.338 AC: 51449 AN: 152012 Hom.: 9600 Cov.: 31 AF XY: 0.331 AC XY: 24586 AN XY: 74278

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.332

Alfa AF: 0.403 Hom.: 14106

Bravo AF: 0.340

Asia WGS AF: 0.163 AC: 572 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.8
DANN	Benign	0.85

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: rs1469513; hg19: chr2-21259562;