Genetic Variant NM_000040.3:c.179+57G>T (chr11-116830953-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000040.3(APOC3):c.179+57G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,070,652 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

APOC3
NM_000040.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.182

Publications

15 publications found

Variant links:

Genes affected

APOC3 (HGNC:610): (apolipoprotein C3) This gene encodes a protein component of triglyceride (TG)-rich lipoproteins (TRLs) including very low density lipoproteins (VLDL), high density lipoproteins (HDL) and chylomicrons. The encoded protein plays a role in role in the metabolism of these TRLs through multiple modes. This protein has been shown to promote the secretion of VLDL1, inhibit lipoprotein lipase enzyme activity, and delay catabolism of TRL remnants. Mutations in this gene are associated with low plasma triglyceride levels and reduced risk of ischemic cardiovascular disease, and hyperalphalipoproteinemia, which is characterized by elevated levels of high density lipoprotein (HDL) and HDL cholesterol in human patients. This gene and other related genes comprise an apolipoprotein gene cluster on chromosome 11. [provided by RefSeq, Sep 2017]

APOC3 Gene-Disease associations (from GenCC):

cholesterol-ester transfer protein deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

APOC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOC3	NM_000040.3 link	c.179+57G>T		intron_variant	Intron 3 of 3	ENST00000227667.8	NP_000031.1	P02656A3KPE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOC3	ENST00000227667.8 link	c.179+57G>T		intron_variant	Intron 3 of 3	1	NM_000040.3	ENSP00000227667.2		P02656

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

112004

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000374

AC:

AN:

1070652

Hom.:

Cov.:

AF XY:

0.00000371

AC XY:

AN XY:

539230

show subpopulations

African (AFR)

AF:

0.0000322

AC:

AN:

31060

American (AMR)

AF:

0.0000255

AC:

AN:

39198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19162

East Asian (EAS)

AF:

0.00

AC:

AN:

30652

South Asian (SAS)

AF:

0.00

AC:

AN:

77908

European-Finnish (FIN)

AF:

0.0000287

AC:

AN:

34896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3650

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

789762

Other (OTH)

AF:

0.0000225

AC:

AN:

44364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

112004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

53410

African (AFR)

AF:

0.00

AC:

AN:

36396

American (AMR)

AF:

0.00

AC:

AN:

9944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2568

East Asian (EAS)

AF:

0.00

AC:

AN:

3726

South Asian (SAS)

AF:

0.00

AC:

AN:

3230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

48964

Other (OTH)

AF:

0.00

AC:

AN:

1480

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.1

(source)

DANN

Benign

0.70

PhyloP100

0.18

PromoterAI

0.033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over