rs9282608

Variant names:

• chr2-21044222-G-A
• rs9282608
• NM_000384.3:c.-277C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-21044222-G-A
• chr2-21044222-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000384.3(APOB):​c.-277C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 269,094 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (150 hom., cov: 32)
  • Exomes 𝑓: 0.012 (40 hom.)
• Consequence: APOB NM_000384.3 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.187

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 2-21044222-G-A is Benign according to our data. Variant chr2-21044222-G-A is described in ClinVar as [Benign]. Clinvar id is 3250494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOB	NM_000384.3	c.-277C>T		upstream_gene_variant		ENST00000233242.5	NP_000375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOB	ENST00000233242.5	c.-277C>T		upstream_gene_variant		1	NM_000384.3	ENSP00000233242.1
APOB	ENST00000673739.2	n.-277C>T		upstream_gene_variant				ENSP00000501110.2
APOB	ENST00000673882.2	n.-277C>T		upstream_gene_variant				ENSP00000501253.2

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4017 AN: 152210 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0254

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.00723

Gnomad FIN AF: 0.00395

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.0119 AC: 1392 AN: 116764 Hom.: 40 AF XY: 0.0111 AC XY: 676 AN XY: 60780

Gnomad4 AFR exome AF: 0.0669

Gnomad4 AMR exome AF: 0.0241

Gnomad4 ASJ exome AF: 0.0131

Gnomad4 EAS exome AF: 0.0822

Gnomad4 SAS exome AF: 0.00278

Gnomad4 FIN exome AF: 0.00218

Gnomad4 NFE exome AF: 0.00122

Gnomad4 OTH exome AF: 0.0127

GnomAD4 genome AF: 0.0266 AC: 4052 AN: 152330 Hom.: 150 Cov.: 32 AF XY: 0.0263 AC XY: 1958 AN XY: 74502

Gnomad4 AFR AF: 0.0715

Gnomad4 AMR AF: 0.0254

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.0813

Gnomad4 SAS AF: 0.00724

Gnomad4 FIN AF: 0.00395

Gnomad4 NFE AF: 0.00148

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0197 Hom.: 7

Bravo AF: 0.0328

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial hypercholesterolemia Benign:1

Jun 23, 2022

GENinCode PLC

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9282608; hg19: chr2-21267094;