rs2266788

Positions:

• chr11-116789970-G-A
• chr11-116789970-G-C

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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -1.13

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=-0.87).
• 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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA5	NM_001371904.1	c.*158C>T		3_prime_UTR_variant	3/3	ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2	c.*158C>T		3_prime_UTR_variant	4/4		NP_001160070.1
APOA5	NM_052968.5	c.*158C>T		3_prime_UTR_variant	4/4		NP_443200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOA5	ENST00000227665.9	c.*158C>T		3_prime_UTR_variant	3/3	1	NM_001371904.1	ENSP00000227665	P1
APOA5	ENST00000433069.2	c.*158C>T		3_prime_UTR_variant	4/4	1		ENSP00000399701	P1
APOA5	ENST00000542499.5	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.: 34

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.: 7 AF XY: 0.897 AC XY: 276126 AN XY: 307894

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.: 34 AF XY: 0.924 AC XY: 68845 AN XY: 74480

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:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

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

Other links and lift over

dbSNP: rs2266788; hg19: chr11-116660686; COSMIC: COSV57065920; COSMIC: COSV57065920;