rs12287066

chr11-116791615-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001371904.1(APOA5):c.132C>A(p.Ile44=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0250

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]

ACMG classification

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	UniProt
APOA5	NM_001371904.1	c.132C>A	p.Ile44=	synonymous_variant	2/3	ENST00000227665.9
APOA5	NM_001166598.2	c.132C>A	p.Ile44=	synonymous_variant	3/4
APOA5	NM_052968.5	c.132C>A	p.Ile44=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOA5	ENST00000227665.9	c.132C>A	p.Ile44=	synonymous_variant	2/3	1	NM_001371904.1	P1
APOA5	ENST00000433069.2	c.132C>A	p.Ile44=	synonymous_variant	3/4	1		P1
APOA5	ENST00000673688.1	c.132C>A	p.Ile44=	synonymous_variant	2/3
APOA5	ENST00000542499.5	c.132C>A	p.Ile44=	synonymous_variant	3/4	5		P1

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 14997 AN: 152162 Hom.: 976 Cov.: 34

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

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.: 33 AF XY: 0.0650 AC XY: 46983 AN XY: 723326

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.: 34 AF XY: 0.0973 AC XY: 7248 AN XY: 74478

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

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	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2018	- -

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

Other links and lift over

dbSNP: rs12287066; hg19: chr11-116662331; COSMIC: COSV57064511; COSMIC: COSV57064511;