Variant chr11-116789970-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001371904.1(APOA5):c.*158C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 737,974 control chromosomes in the GnomAD database, including 305,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 65882 hom., cov: 34)

Exomes 𝑓: 0.90 ( 239152 hom. )

Consequence

APOA5
NM_001371904.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -1.13

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=-0.87).

BP6

Variant 11-116789970-G-A is Benign according to our data. Variant chr11-116789970-G-A is described in ClinVar as [Benign]. Clinvar id is 127141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116789970-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
APOA5	NM_001371904.1 linkuse as main transcript	c.*158C>T	3_prime_UTR_variant	3/3	ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2 linkuse as main transcript	c.*158C>T	3_prime_UTR_variant	4/4		NP_001160070.1
APOA5	NM_052968.5 linkuse as main transcript	c.*158C>T	3_prime_UTR_variant	4/4		NP_443200.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
APOA5	ENST00000227665.9 linkuse as main transcript	c.*158C>T	3_prime_UTR_variant	3/3	1	NM_001371904.1	ENSP00000227665	P1
APOA5	ENST00000433069.2 linkuse as main transcript	c.*158C>T	3_prime_UTR_variant	4/4	1		ENSP00000399701	P1
APOA5	ENST00000542499.5 linkuse as main transcript	c.*158C>T	3_prime_UTR_variant	4/4	5		ENSP00000445002	P1

Frequencies

GnomAD3 genomes

AF:

0.928

AC:

141285

AN:

152200

Hom.:

65830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.984

Gnomad AMI

AF:

0.897

Gnomad AMR

AF:

0.888

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

0.770

Gnomad SAS

AF:

0.791

Gnomad FIN

AF:

0.917

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.929

Gnomad OTH

AF:

0.917

GnomAD4 exome

AF:

0.901

AC:

527921

AN:

585656

Hom.:

239152

Cov.:

AF XY:

0.897

AC XY:

276126

AN XY:

307894

show subpopulations

Gnomad4 AFR exome

AF:

0.986

Gnomad4 AMR exome

AF:

0.842

Gnomad4 ASJ exome

AF:

0.910

Gnomad4 EAS exome

AF:

0.749

Gnomad4 SAS exome

AF:

0.798

Gnomad4 FIN exome

AF:

0.917

Gnomad4 NFE exome

AF:

0.930

Gnomad4 OTH exome

AF:

0.906

GnomAD4 genome

AF:

0.928

AC:

141392

AN:

152318

Hom.:

65882

Cov.:

AF XY:

0.924

AC XY:

68845

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.984

Gnomad4 AMR

AF:

0.887

Gnomad4 ASJ

AF:

0.910

Gnomad4 EAS

AF:

0.769

Gnomad4 SAS

AF:

0.791

Gnomad4 FIN

AF:

0.917

Gnomad4 NFE

AF:

0.929

Gnomad4 OTH

AF:

0.912

Alfa

AF:

0.923

Hom.:

109288

Bravo

AF:

0.929

Asia WGS

AF:

0.798

AC:

2778

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	This variant is associated with the following publications: (PMID: 21386085, 29237685, 25151233, 25034063, 11588264, 24387992) -

Hypertriglyceridemia 1

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jan 02, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.23

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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