rs11568822

Positions:

• chr19-44914381-C-CTTCG

Variant summary

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

The ENST00000588750.5(APOC1):​c.-189_-188insCGTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 154,660 control chromosomes in the GnomAD database, including 4,113 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4075 hom., cov: 24)
  • Exomes 𝑓: 0.14 (38 hom.)
• Consequence: APOC1 ENST00000588750.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

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 (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOC1	NM_001321065.2	c.-127_-126insCGTT		5_prime_UTR_variant	1/4		NP_001307994.1
APOC1	NM_001321066.2	c.-189_-188insCGTT		5_prime_UTR_variant	1/5		NP_001307995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOC1	ENST00000588750.5	c.-189_-188insCGTT		5_prime_UTR_variant	1/5	1		ENSP00000465356	P1
APOC1	ENST00000588802.5	c.-127_-126insCGTT		5_prime_UTR_variant	1/4	1		ENSP00000468029	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34107 AN: 151658 Hom.: 4065 Cov.: 24

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.140 AC: 404 AN: 2884 Hom.: 38 Cov.: 0 AF XY: 0.145 AC XY: 225 AN XY: 1550

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.0610

Gnomad4 SAS exome AF: 0.0811

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.0878

GnomAD4 genome AF: 0.225 AC: 34155 AN: 151776 Hom.: 4075 Cov.: 24 AF XY: 0.224 AC XY: 16577 AN XY: 74170

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.195

Alfa AF: 0.222 Hom.: 339

Asia WGS AF: 0.246 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11568822; hg19: chr19-45417638;