rs11568822

Variant names:

• chr19-44914381-C-CTTCG
• rs11568822
• ENST00000588750.5:c.-189_-188insCGTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001321065.2(APOC1):​c.-127_-126insCGTT 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 NM_001321065.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 22 publications found

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]

ENSG00000280087 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321065.2. 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
	APOC1	NM_001321065.2		c.-127_-126insCGTT		5_prime_UTR	Exon 1 of 4	NP_001307994.1	P02654
	APOC1	NM_001321066.2		c.-189_-188insCGTT		5_prime_UTR	Exon 1 of 5	NP_001307995.1	P02654
	APOC1	NM_001645.5	MANE Select	c.-373_-372insTTCG		upstream_gene	N/A	NP_001636.1	P02654

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC1	ENST00000588750.5	TSL:1	c.-189_-188insCGTT		5_prime_UTR	Exon 1 of 5	ENSP00000465356.1	P02654
	APOC1	ENST00000588802.5	TSL:1	c.-127_-126insCGTT		5_prime_UTR	Exon 1 of 4	ENSP00000468029.1	P02654
	APOC1	ENST00000928314.1		c.-125_-124insCGTT		5_prime_UTR	Exon 1 of 4	ENSP00000598373.1

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

African (AFR) AF: 0.159 AC: 7 AN: 44

American (AMR) AF: 0.108 AC: 68 AN: 628

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 6 AN: 28

East Asian (EAS) AF: 0.0610 AC: 10 AN: 164

South Asian (SAS) AF: 0.0811 AC: 24 AN: 296

European-Finnish (FIN) AF: 0.136 AC: 6 AN: 44

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.177 AC: 270 AN: 1524

Other (OTH) AF: 0.0878 AC: 13 AN: 148

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

African (AFR) AF: 0.293 AC: 12100 AN: 41318

American (AMR) AF: 0.129 AC: 1964 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3472

East Asian (EAS) AF: 0.181 AC: 930 AN: 5152

South Asian (SAS) AF: 0.140 AC: 676 AN: 4820

European-Finnish (FIN) AF: 0.234 AC: 2460 AN: 10528

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14771 AN: 67916

Other (OTH) AF: 0.195 AC: 412 AN: 2110

Alfa AF: 0.222 Hom.: 339

Asia WGS AF: 0.246 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11568822; hg19: chr19-45417638;