rs7256684

Variant names:

• chr19-44948185-A-G
• rs7256684
• NM_000483.5:c.-13-281A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-44948185-A-G
• chr19-44948185-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000483.5(APOC2):​c.-13-281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 313,086 control chromosomes in the GnomAD database, including 41,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21621 hom., cov: 32)
  • Exomes 𝑓: 0.49 (20048 hom.)
• Consequence: APOC2 NM_000483.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.36
• Publications: 8 publications found

Genes affected

APOC2 (HGNC:609): (apolipoprotein C2) This gene encodes a lipid-binding protein belonging to the apolipoprotein gene family. The protein is secreted in plasma where it is a component of very low density lipoprotein. This protein activates the enzyme lipoprotein lipase, which hydrolyzes triglycerides and thus provides free fatty acids for cells. Mutations in this gene cause hyperlipoproteinemia type IB, characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis. This gene is present in a cluster with other related apolipoprotein genes on chromosome 19. Naturally occurring read-through transcription exists between this gene and the neighboring upstream apolipoprotein C-IV (APOC4) gene. [provided by RefSeq, Mar 2011]

APOC4-APOC2 (HGNC:44426): (APOC4-APOC2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring apolipoprotein C-IV (APOC4) and apolipoprotein C-II (APOC2) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 19-44948185-A-G is Benign according to our data. Variant chr19-44948185-A-G is described in ClinVar as Benign. ClinVar VariationId is 1281172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000483.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC2	NM_000483.5	MANE Select	c.-13-281A>G		intron	N/A	NP_000474.2
	APOC4-APOC2	NR_037932.1		n.1195-281A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC2	ENST00000252490.7	TSL:2 MANE Select	c.-13-281A>G		intron	N/A	ENSP00000252490.5	P02655
	APOC4-APOC2	ENST00000589057.5	TSL:5	c.219-281A>G		intron	N/A	ENSP00000468139.1	K7ER74
	APOC2	ENST00000896547.1		c.-294A>G		5_prime_UTR	Exon 1 of 3	ENSP00000566606.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79725 AN: 151704 Hom.: 21588 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.489 AC: 78838 AN: 161264 Hom.: 20048 AF XY: 0.496 AC XY: 43320 AN XY: 87406

African (AFR) AF: 0.616 AC: 3035 AN: 4928

American (AMR) AF: 0.619 AC: 5489 AN: 8862

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1831 AN: 4020

East Asian (EAS) AF: 0.521 AC: 3929 AN: 7538

South Asian (SAS) AF: 0.568 AC: 15582 AN: 27456

European-Finnish (FIN) AF: 0.500 AC: 3263 AN: 6520

Middle Eastern (MID) AF: 0.446 AC: 241 AN: 540

European-Non Finnish (NFE) AF: 0.446 AC: 41538 AN: 93230

Other (OTH) AF: 0.481 AC: 3930 AN: 8170

GnomAD4 genome AF: 0.526 AC: 79808 AN: 151822 Hom.: 21621 Cov.: 32 AF XY: 0.528 AC XY: 39167 AN XY: 74198

African (AFR) AF: 0.630 AC: 26060 AN: 41360

American (AMR) AF: 0.577 AC: 8794 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1569 AN: 3466

East Asian (EAS) AF: 0.557 AC: 2870 AN: 5156

South Asian (SAS) AF: 0.584 AC: 2808 AN: 4810

European-Finnish (FIN) AF: 0.489 AC: 5167 AN: 10562

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30973 AN: 67916

Other (OTH) AF: 0.504 AC: 1062 AN: 2108

Alfa AF: 0.505 Hom.: 2479

Bravo AF: 0.534

Asia WGS AF: 0.580 AC: 2016 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.047
DANN	Benign	0.47
PhyloP100		-3.4
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7256684; hg19: chr19-45451442;