11-116791691-G-C

Variant summary

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

The NM_001371904.1(APOA5):c.56C>G(p.Ser19Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0624 in 1,607,778 control chromosomes in the GnomAD database, including 3,555 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S19L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.065 ( 352 hom., cov: 34)

Exomes 𝑓: 0.062 ( 3203 hom. )

Consequence

APOA5
NM_001371904.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 1.58

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 (MetaRNN=0.0018840134).

BP6

Variant 11-116791691-G-C is Benign according to our data. Variant chr11-116791691-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 4403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116791691-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
APOA5	NM_001371904.1 linkuse as main transcript	c.56C>G	p.Ser19Trp	missense_variant	2/3	ENST00000227665.9
APOA5	NM_001166598.2 linkuse as main transcript	c.56C>G	p.Ser19Trp	missense_variant	3/4
APOA5	NM_052968.5 linkuse as main transcript	c.56C>G	p.Ser19Trp	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
APOA5	ENST00000227665.9 linkuse as main transcript	c.56C>G	p.Ser19Trp	missense_variant	2/3	1	NM_001371904.1	P1
APOA5	ENST00000433069.2 linkuse as main transcript	c.56C>G	p.Ser19Trp	missense_variant	3/4	1		P1
APOA5	ENST00000673688.1 linkuse as main transcript	c.56C>G	p.Ser19Trp	missense_variant	2/3
APOA5	ENST00000542499.5 linkuse as main transcript	c.56C>G	p.Ser19Trp	missense_variant	3/4	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0649

AC:

9872

AN:

152200

Hom.:

349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0619

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0405

Gnomad FIN

AF:

0.0551

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0628

Gnomad OTH

AF:

0.0779

GnomAD3 exomes

AF:

0.0684

AC:

16228

AN:

237114

Hom.:

719

AF XY:

0.0645

AC XY:

8284

AN XY:

128364

show subpopulations

Gnomad AFR exome

AF:

0.0635

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.0681

Gnomad EAS exome

AF:

0.000286

Gnomad SAS exome

AF:

0.0374

Gnomad FIN exome

AF:

0.0608

Gnomad NFE exome

AF:

0.0640

Gnomad OTH exome

AF:

0.0701

GnomAD4 exome

AF:

0.0621

AC:

90359

AN:

1455460

Hom.:

3203

Cov.:

AF XY:

0.0610

AC XY:

44118

AN XY:

723514

show subpopulations

Gnomad4 AFR exome

AF:

0.0645

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.0653

Gnomad4 EAS exome

AF:

0.000559

Gnomad4 SAS exome

AF:

0.0387

Gnomad4 FIN exome

AF:

0.0626

Gnomad4 NFE exome

AF:

0.0627

Gnomad4 OTH exome

AF:

0.0606

GnomAD4 genome

AF:

0.0649

AC:

9890

AN:

152318

Hom.:

352

Cov.:

AF XY:

0.0642

AC XY:

4778

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0619

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0408

Gnomad4 FIN

AF:

0.0551

Gnomad4 NFE

AF:

0.0628

Gnomad4 OTH

AF:

0.0776

Alfa

AF:

0.0542

Hom.:

191

Bravo

AF:

0.0704

TwinsUK

AF:

0.0620

AC:

230

ALSPAC

AF:

0.0643

AC:

248

ESP6500AA

AF:

0.0611

AC:

269

ESP6500EA

AF:

0.0649

AC:

558

ExAC

AF:

0.0620

AC:

7527

Asia WGS

AF:

0.0300

AC:

104

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jul 18, 2023

- -

Familial type 5 hyperlipoproteinemia;C5444012:Hypertriglyceridemia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 07, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

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. -

Hypertriglyceridemia 1

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Nov 15, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.23

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.48

T;T;.

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.70

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

2.0

M;M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.43

MPC

1.5

ClinPred

0.017

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.098

gMVP

0.42

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