rs7257095

Variant names:

• chr19-44948390-C-G
• rs7257095
• NM_000483.5:c.-13-76C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-44948390-C-G
• chr19-44948390-C-A
• chr19-44948390-C-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.-13-76C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,266,596 control chromosomes in the GnomAD database, including 597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (267 hom., cov: 32)
  • Exomes 𝑓: 0.013 (330 hom.)
• Consequence: APOC2 NM_000483.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.42
• Publications: 2 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=-0.91).
• BP6: Variant 19-44948390-C-G is Benign according to our data. Variant chr19-44948390-C-G is described in ClinVar as Benign. ClinVar VariationId is 1268118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 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.-13-76C>G		intron	N/A	NP_000474.2
	APOC4-APOC2	NR_037932.1		n.1195-76C>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.-13-76C>G		intron	N/A	ENSP00000252490.5	P02655
	APOC4-APOC2	ENST00000589057.5	TSL:5	c.219-76C>G		intron	N/A	ENSP00000468139.1	K7ER74
	APOC2	ENST00000896559.1		c.-89C>G		5_prime_UTR	Exon 3 of 5	ENSP00000566618.1

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5924 AN: 152074 Hom.: 267 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00907

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.0130 AC: 14513 AN: 1114404 Hom.: 330 Cov.: 16 AF XY: 0.0140 AC XY: 7991 AN XY: 569982

African (AFR) AF: 0.112 AC: 2913 AN: 26120

American (AMR) AF: 0.0110 AC: 484 AN: 44108

Ashkenazi Jewish (ASJ) AF: 0.00326 AC: 78 AN: 23914

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 38094

South Asian (SAS) AF: 0.0482 AC: 3792 AN: 78624

European-Finnish (FIN) AF: 0.00293 AC: 155 AN: 52982

Middle Eastern (MID) AF: 0.0256 AC: 129 AN: 5048

European-Non Finnish (NFE) AF: 0.00772 AC: 6150 AN: 796414

Other (OTH) AF: 0.0165 AC: 811 AN: 49100

GnomAD4 genome AF: 0.0390 AC: 5937 AN: 152192 Hom.: 267 Cov.: 32 AF XY: 0.0384 AC XY: 2858 AN XY: 74418

African (AFR) AF: 0.113 AC: 4677 AN: 41490

American (AMR) AF: 0.0190 AC: 290 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0533 AC: 257 AN: 4820

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00907 AC: 617 AN: 68012

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.00816 Hom.: 5

Bravo AF: 0.0425

Asia WGS AF: 0.0190 AC: 66 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	-0.91
CADD	Benign	0.16
DANN	Benign	0.45
PhyloP100		-1.4
PromoterAI		-0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7257095; hg19: chr19-45451647;