dbSNP rs584007: APOC1:c.-304+9A>G (chr19-44913221-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000876409.1(APOC1):c.-304+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,132 control chromosomes in the GnomAD database, including 35,687 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 35652 hom., cov: 30)

Exomes 𝑓: 0.61 ( 35 hom. )

Consequence

APOC1
ENST00000876409.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.720

Publications

43 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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new If you want to explore the variant's impact on the transcript ENST00000876409.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000876409.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC1	ENST00000876409.1		c.-304+9A>G		intron	N/A	ENSP00000546468.1
	ENSG00000280087	ENST00000623895.1	TSL:6	n.3847A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.672

AC:

102064

AN:

151860

Hom.:

35593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.854

Gnomad AMI

AF:

0.649

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.574

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.730

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.633

Gnomad OTH

AF:

0.642

GnomAD4 exome

AF:

0.610

AC:

AN:

154

Hom.:

Cov.:

AF XY:

0.597

AC XY:

AN XY:

124

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.619

AC:

AN:

126

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.672

AC:

102191

AN:

151978

Hom.:

35652

Cov.:

AF XY:

0.669

AC XY:

49716

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.854

AC:

35406

AN:

41474

American (AMR)

AF:

0.503

AC:

7675

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.574

AC:

1992

AN:

3468

East Asian (EAS)

AF:

0.424

AC:

2172

AN:

5118

South Asian (SAS)

AF:

0.443

AC:

2139

AN:

4826

European-Finnish (FIN)

AF:

0.730

AC:

7718

AN:

10574

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.633

AC:

42991

AN:

67940

Other (OTH)

AF:

0.646

AC:

1361

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1620

3240

4859

6479

8099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.654

Hom.:

36712

Bravo

AF:

0.665

Asia WGS

AF:

0.543

AC:

1892

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.86

(source)

DANN

Benign

0.60

PhyloP100

-0.72

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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