11-116790772-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001371904.1(APOA5):c.457G>A(p.Val153Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 1,613,350 control chromosomes in the GnomAD database, including 2,075 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V153V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.056 ( 332 hom., cov: 34)

Exomes 𝑓: 0.037 ( 1743 hom. )

Consequence

APOA5
NM_001371904.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.21

Publications

64 publications found

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 Gene-Disease associations (from GenCC):

hypertriglyceridemia 1
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
hyperlipoproteinemia type V
Inheritance: AD, SD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

APOA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016683042).

BP6

Variant 11-116790772-C-T is Benign according to our data. Variant chr11-116790772-C-T is described in ClinVar as Benign. ClinVar VariationId is 496496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
APOA5	NM_001371904.1 link	c.457G>A	p.Val153Met	missense_variant	Exon 3 of 3	ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2 link	c.457G>A	p.Val153Met	missense_variant	Exon 4 of 4		NP_001160070.1
APOA5	NM_052968.5 link	c.457G>A	p.Val153Met	missense_variant	Exon 4 of 4		NP_443200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
APOA5	ENST00000227665.9 link	c.457G>A	p.Val153Met	missense_variant	Exon 3 of 3	1	NM_001371904.1	ENSP00000227665.4
APOA5	ENST00000433069.2 link	c.457G>A	p.Val153Met	missense_variant	Exon 4 of 4	1		ENSP00000399701.2
APOA5	ENST00000673688.1 link	c.541G>A	p.Val181Met	missense_variant	Exon 3 of 3			ENSP00000501141.1
APOA5	ENST00000542499.5 link	c.457G>A	p.Val153Met	missense_variant	Exon 4 of 4	5		ENSP00000445002.1

Frequencies

GnomAD3 genomes

AF:

0.0561

AC:

8542

AN:

152156

Hom.:

328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0901

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0653

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.0696

Gnomad FIN

AF:

0.0512

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.0526

GnomAD2 exomes

AF:

0.0503

AC:

12596

AN:

250602

AF XY:

0.0500

show subpopulations

Gnomad AFR exome

AF:

0.0923

Gnomad AMR exome

AF:

0.0457

Gnomad ASJ exome

AF:

0.0388

Gnomad EAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.0493

Gnomad NFE exome

AF:

0.0292

Gnomad OTH exome

AF:

0.0473

GnomAD4 exome

AF:

0.0369

AC:

53912

AN:

1461076

Hom.:

1743

Cov.:

AF XY:

0.0383

AC XY:

27822

AN XY:

726908

show subpopulations

African (AFR)

AF:

0.0908

AC:

3041

AN:

33478

American (AMR)

AF:

0.0471

AC:

2106

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0403

AC:

1054

AN:

26132

East Asian (EAS)

AF:

0.178

AC:

7057

AN:

39696

South Asian (SAS)

AF:

0.0763

AC:

6585

AN:

86258

European-Finnish (FIN)

AF:

0.0479

AC:

2521

AN:

52662

Middle Eastern (MID)

AF:

0.0674

AC:

389

AN:

5768

European-Non Finnish (NFE)

AF:

0.0255

AC:

28401

AN:

1111974

Other (OTH)

AF:

0.0457

AC:

2758

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

3798

7596

11394

15192

18990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1234

2468

3702

4936

6170

<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:

0.0562

AC:

8559

AN:

152274

Hom.:

332

Cov.:

AF XY:

0.0595

AC XY:

4433

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0901

AC:

3746

AN:

41560

American (AMR)

AF:

0.0651

AC:

997

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3470

East Asian (EAS)

AF:

0.129

AC:

667

AN:

5166

South Asian (SAS)

AF:

0.0700

AC:

338

AN:

4826

European-Finnish (FIN)

AF:

0.0512

AC:

544

AN:

10624

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0287

AC:

1954

AN:

68004

Other (OTH)

AF:

0.0530

AC:

112

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

414

828

1242

1656

2070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0388

Hom.:

358

Bravo

AF:

0.0561

TwinsUK

AF:

0.0213

AC:

ALSPAC

AF:

0.0231

AC:

ESP6500AA

AF:

0.0841

AC:

370

ESP6500EA

AF:

0.0290

AC:

249

ExAC

AF:

0.0514

AC:

6237

Asia WGS

AF:

0.113

AC:

391

AN:

3478

EpiCase

AF:

0.0309

EpiControl

AF:

0.0289

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 19, 2017

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: The APOA5 c.457G>A (p.Val153Met) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict benign outcome for this variant. This variant was found in 6280/120674 control chromosomes (262 homozygotes) including ExAC at a frequency of 0.052041, which is approximately 781 times the estimated maximal expected allele frequency of a pathogenic APOA5 variant (0.0000667), suggesting this variant is likely a benign polymorphism. In addition, this variant was not found to confer increased risk of hypertriglyceridemia in a case-control study (Kao_2003). Taken together, this variant is classified as benign. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 31619059, 30420299, 28548292, 21423763) -

Cardiovascular phenotype

Benign:1

Jan 26, 2019

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.28

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.23

T;T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.72

.;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L;.

PhyloP100

-2.2

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.090

N;N;N

REVEL

Benign

0.079

Sift

Benign

0.11

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.044

B;B;.

Vest4

0.015

MPC

0.54

ClinPred

0.0029

GERP RS

-4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.038

gMVP

0.59

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over