rs2266788

Variant names:

• chr11-116789970-G-A
• rs2266788
• NM_001371904.1:c.*158C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 175 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 127141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
APOA5	NM_001371904.1	c.*158C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2	c.*158C>T		3_prime_UTR_variant	Exon 4 of 4		NP_001160070.1
APOA5	NM_052968.5	c.*158C>T		3_prime_UTR_variant	Exon 4 of 4		NP_443200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA5	ENST00000227665.9	c.*158C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_001371904.1	ENSP00000227665.4
APOA5	ENST00000433069.2	c.*158C>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000399701.2
APOA5	ENST00000542499.5	c.*158C>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000445002.1
APOA5	ENST00000673688.1	c.*158C>T		downstream_gene_variant				ENSP00000501141.1

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

African (AFR) AF: 0.986 AC: 15606 AN: 15832

American (AMR) AF: 0.842 AC: 24434 AN: 29020

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 15773 AN: 17332

East Asian (EAS) AF: 0.749 AC: 23834 AN: 31834

South Asian (SAS) AF: 0.798 AC: 45551 AN: 57048

European-Finnish (FIN) AF: 0.917 AC: 32570 AN: 35508

Middle Eastern (MID) AF: 0.896 AC: 2139 AN: 2386

European-Non Finnish (NFE) AF: 0.930 AC: 340011 AN: 365772

Other (OTH) AF: 0.906 AC: 28003 AN: 30924

GnomAD4 genome AF: 0.928 AC: 141392 AN: 152318 Hom.: 65882 Cov.: 34 AF XY: 0.924 AC XY: 68845 AN XY: 74480

African (AFR) AF: 0.984 AC: 40914 AN: 41574

American (AMR) AF: 0.887 AC: 13580 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3159 AN: 3472

East Asian (EAS) AF: 0.769 AC: 3975 AN: 5170

South Asian (SAS) AF: 0.791 AC: 3821 AN: 4832

European-Finnish (FIN) AF: 0.917 AC: 9741 AN: 10624

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.929 AC: 63191 AN: 68022

Other (OTH) AF: 0.912 AC: 1930 AN: 2116

Alfa AF: 0.923 Hom.: 250440

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21386085, 29237685, 25151233, 25034063, 11588264, 24387992) -

Hypertriglyceridemia 1 Other:1

Jan 02, 2014

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.23
DANN	Benign	0.56
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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