Genetic Variant NM_001645.5: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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001645.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
APOC1	NM_001645.5	MANE Select	c.195-457delG	intron	N/A	NP_001636.1
APOC1	NM_001379687.1		c.340-457delG	intron	N/A	NP_001366616.1
APOC1	NM_001321065.2		c.195-457delG	intron	N/A	NP_001307994.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
APOC1	ENST00000592535.6	TSL:1 MANE Select	c.195-457delG	intron	N/A	ENSP00000468276.2
APOC1	ENST00000588750.5	TSL:1	c.195-457delG	intron	N/A	ENSP00000465356.1
APOC1	ENST00000588802.5	TSL:1	c.195-457delG	intron	N/A	ENSP00000468029.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over