rs12721052

Positions:

• chr19-44918715-AG-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000592535.6(APOC1):​c.195-457del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 157,762 control chromosomes in the GnomAD database, including 7,439 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (7156 hom., cov: 0)
  • Exomes 𝑓: 0.26 (283 hom.)
• Consequence: APOC1 ENST00000592535.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

Genes affected

APOC1 (HGNC:607): (apolipoprotein C1) This gene encodes a member of the apolipoprotein C1 family. This gene is expressed primarily in the liver, and it is activated when monocytes differentiate into macrophages. The encoded protein plays a central role in high density lipoprotein (HDL) and very low density lipoprotein (VLDL) metabolism. This protein has also been shown to inhibit cholesteryl ester transfer protein in plasma. A pseudogene of this gene is located 4 kb downstream in the same orientation, on the same chromosome. This gene is mapped to chromosome 19, where it resides within a apolipoprotein gene cluster. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOC1	NM_001645.5	c.195-457del		intron_variant		ENST00000592535.6	NP_001636.1
APOC1	NM_001321065.2	c.195-457del		intron_variant			NP_001307994.1
APOC1	NM_001321066.2	c.195-457del		intron_variant			NP_001307995.1
APOC1	NM_001379687.1	c.340-457del		intron_variant			NP_001366616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOC1	ENST00000592535.6	c.195-457del		intron_variant		1	NM_001645.5	ENSP00000468276	P1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46244 AN: 150710 Hom.: 7157 Cov.: 0

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.260 AC: 1800 AN: 6934 Hom.: 283 AF XY: 0.262 AC XY: 953 AN XY: 3632

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.307 AC: 46259 AN: 150828 Hom.: 7156 Cov.: 0 AF XY: 0.306 AC XY: 22495 AN XY: 73630

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.338

Alfa AF: 0.176 Hom.: 330

Bravo AF: 0.297

Asia WGS AF: 0.228 AC: 793 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs12721052; hg19: chr19-45421972;