dbSNP rs11568822: APOC1:c.-189_-188insCGTT (chr19-44914381-C-CTTCG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.342

Publications

22 publications found

Variant links:

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]

APOC1 links:

ENSG00000280087 (HGNC:):

ENSG00000280087 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
APOC1	NM_001321065.2 link	c.-127_-126insCGTT	5_prime_UTR_variant	Exon 1 of 4		NP_001307994.1
APOC1	NM_001321066.2 link	c.-189_-188insCGTT	5_prime_UTR_variant	Exon 1 of 5		NP_001307995.1
APOC1	NM_001645.5 link	c.-373_-372insTTCG	upstream_gene_variant		ENST00000592535.6	NP_001636.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
APOC1	ENST00000588750.5 link	c.-189_-188insCGTT	5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000465356.1
APOC1	ENST00000588802.5 link	c.-127_-126insCGTT	5_prime_UTR_variant	Exon 1 of 4	1		ENSP00000468029.1
ENSG00000280087	ENST00000623895.1 link	n.5009_5010insCGTT	non_coding_transcript_exon_variant	Exon 1 of 1	6
APOC1	ENST00000592535.6 link	c.-373_-372insTTCG	upstream_gene_variant		1	NM_001645.5	ENSP00000468276.2

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34107

AN:

151658

Hom.:

4065

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.145

AC XY:

225

AN XY:

1550

show subpopulations

African (AFR)

AF:

0.159

AC:

AN:

American (AMR)

AF:

0.108

AC:

AN:

628

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

AN:

East Asian (EAS)

AF:

0.0610

AC:

AN:

164

South Asian (SAS)

AF:

0.0811

AC:

AN:

296

European-Finnish (FIN)

AF:

0.136

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.177

AC:

270

AN:

1524

Other (OTH)

AF:

0.0878

AC:

AN:

148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.225

AC:

34155

AN:

151776

Hom.:

4075

Cov.:

AF XY:

0.224

AC XY:

16577

AN XY:

74170

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14771

AN:

67916

Other (OTH)

AF:

0.195

AC:

412

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1360

2720

4081

5441

6801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.34

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over