dbSNP rs12721052: APOC1:c.195-457delG (chr19-44918715-AG-A) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_001645.5(APOC1):c.195-457delG 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
NM_001645.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.293

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
APOC1	NM_001645.5 link	c.195-457delG	intron_variant	Intron 3 of 3	ENST00000592535.6	NP_001636.1	P02654A0A024R0T8
APOC1	NM_001379687.1 link	c.340-457delG	intron_variant	Intron 3 of 3		NP_001366616.1
APOC1	NM_001321065.2 link	c.195-457delG	intron_variant	Intron 3 of 3		NP_001307994.1	P02654A0A024R0T8
APOC1	NM_001321066.2 link	c.195-457delG	intron_variant	Intron 4 of 4		NP_001307995.1	P02654A0A024R0T8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOC1	ENST00000592535.6 link	c.195-457delG		intron_variant	Intron 3 of 3	1	NM_001645.5	ENSP00000468276.2		P02654K7ERI9

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46244

AN:

150710

Hom.:

7157

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

144

American (AMR)

AF:

0.206

AC:

119

AN:

578

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

AN:

144

East Asian (EAS)

AF:

0.211

AC:

AN:

218

South Asian (SAS)

AF:

0.183

AC:

AN:

514

European-Finnish (FIN)

AF:

0.337

AC:

AN:

264

Middle Eastern (MID)

AF:

0.346

AC:

AN:

European-Non Finnish (NFE)

AF:

0.273

AC:

1276

AN:

4678

Other (OTH)

AF:

0.277

AC:

102

AN:

368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

127

191

254

318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.307

AC:

46259

AN:

150828

Hom.:

7156

Cov.:

AF XY:

0.306

AC XY:

22495

AN XY:

73630

show subpopulations

African (AFR)

AF:

0.237

AC:

9722

AN:

40954

American (AMR)

AF:

0.295

AC:

4458

AN:

15130

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1144

AN:

3466

East Asian (EAS)

AF:

0.212

AC:

1075

AN:

5074

South Asian (SAS)

AF:

0.275

AC:

1310

AN:

4770

European-Finnish (FIN)

AF:

0.372

AC:

3851

AN:

10364

Middle Eastern (MID)

AF:

0.255

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.347

AC:

23507

AN:

67788

Other (OTH)

AF:

0.338

AC:

706

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1547

3094

4640

6187

7734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.176

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

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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