rs12287066

Positions:

chr11-116791615-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001371904.1(APOA5):c.132C>A(p.Ile44Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 1,607,526 control chromosomes in the GnomAD database, including 4,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.099 ( 981 hom., cov: 34)

Exomes 𝑓: 0.067 ( 3833 hom. )

Consequence

APOA5
NM_001371904.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0250

Variant links:

Genes affected

APOA5 (HGNC:17288): (apolipoprotein A5) The protein encoded by this gene is an apolipoprotein that plays an important role in regulating the plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of high density lipoprotein and is highly similar to a rat protein that is upregulated in response to liver injury. Mutations in this gene have been associated with hypertriglyceridemia and hyperlipoproteinemia type 5. This gene is located proximal to the apolipoprotein gene cluster on chromosome 11q23. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Oct 2009]

APOA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 11-116791615-G-T is Benign according to our data. Variant chr11-116791615-G-T is described in ClinVar as [Benign]. Clinvar id is 496495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116791615-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA5	NM_001371904.1 link	c.132C>A	p.Ile44Ile	synonymous_variant	2/3	ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2 link	c.132C>A	p.Ile44Ile	synonymous_variant	3/4		NP_001160070.1	Q6Q788A0A0B4RUS7
APOA5	NM_052968.5 link	c.132C>A	p.Ile44Ile	synonymous_variant	3/4		NP_443200.2	Q6Q788A0A0B4RUS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
APOA5	ENST00000227665.9 link	c.132C>A	p.Ile44Ile	synonymous_variant	2/3	1	NM_001371904.1	ENSP00000227665.4	Q6Q788
APOA5	ENST00000433069.2 link	c.132C>A	p.Ile44Ile	synonymous_variant	3/4	1		ENSP00000399701.2	Q6Q788
APOA5	ENST00000673688.1 link	c.132C>A	p.Ile44Ile	synonymous_variant	2/3			ENSP00000501141.1	A0A669KB69
APOA5	ENST00000542499.5 link	c.132C>A	p.Ile44Ile	synonymous_variant	3/4	5		ENSP00000445002.1	Q6Q788

Frequencies

GnomAD3 genomes

AF:

0.0986

AC:

14997

AN:

152162

Hom.:

976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0741

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0416

Gnomad FIN

AF:

0.0554

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0644

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.0773

AC:

18496

AN:

239316

Hom.:

1001

AF XY:

0.0713

AC XY:

9223

AN XY:

129412

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.0738

Gnomad EAS exome

AF:

0.000282

Gnomad SAS exome

AF:

0.0387

Gnomad FIN exome

AF:

0.0606

Gnomad NFE exome

AF:

0.0649

Gnomad OTH exome

AF:

0.0758

GnomAD4 exome

AF:

0.0665

AC:

96790

AN:

1455246

Hom.:

3833

Cov.:

AF XY:

0.0650

AC XY:

46983

AN XY:

723326

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.0710

Gnomad4 EAS exome

AF:

0.000559

Gnomad4 SAS exome

AF:

0.0401

Gnomad4 FIN exome

AF:

0.0628

Gnomad4 NFE exome

AF:

0.0639

Gnomad4 OTH exome

AF:

0.0685

GnomAD4 genome

AF:

0.0986

AC:

15020

AN:

152280

Hom.:

981

Cov.:

AF XY:

0.0973

AC XY:

7248

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.175

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.0741

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0418

Gnomad4 FIN

AF:

0.0554

Gnomad4 NFE

AF:

0.0644

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.0782

Hom.:

291

Bravo

AF:

0.109

Asia WGS

AF:

0.0370

AC:

128

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 19, 2017	Variant summary: The APOA5 c.132C>A (p.Ile44Ile) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of SRp40. However, these predictions have yet to be confirmed by functional studies. This variant was found in 8225/74964 control chromosomes (443 homozygotes) from ExAC at a frequency of 0.1097193, which is approximately 1646 times the estimated maximal expected allele frequency of a pathogenic APOA5 variant (0.0000667), thus this variant is a common benign polymorphism. Taken together, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 11, 2019

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.7

DANN

Benign

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over