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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371904.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA5	NM_001371904.1	MANE Select	c.*158C>T		3_prime_UTR	Exon 3 of 3	NP_001358833.1	Q6Q788
	APOA5	NM_001166598.2		c.*158C>T		3_prime_UTR	Exon 4 of 4	NP_001160070.1	A0A0B4RUS7
	APOA5	NM_052968.5		c.*158C>T		3_prime_UTR	Exon 4 of 4	NP_443200.2	Q6Q788

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA5	ENST00000227665.9	TSL:1 MANE Select	c.*158C>T		3_prime_UTR	Exon 3 of 3	ENSP00000227665.4	Q6Q788
	APOA5	ENST00000433069.2	TSL:1	c.*158C>T		3_prime_UTR	Exon 4 of 4	ENSP00000399701.2	Q6Q788
	APOA5	ENST00000873020.1		c.*158C>T		3_prime_UTR	Exon 4 of 4	ENSP00000543079.1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	-	Hypertriglyceridemia 1 (1)

Computational scores

Source: dbNSFP v4.9

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;