11-116791110-T-C

Variant names:

• chr11-116791110-T-C
• rs2072560
• NM_001371904.1:c.162-43A>G

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.162-43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,492,902 control chromosomes in the GnomAD database, including 640,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66650 hom., cov: 33)
  • Exomes 𝑓: 0.92 (573892 hom.)
• Consequence: APOA5 NM_001371904.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.540
• Publications: 58 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=-0.8).
• BP6: Variant 11-116791110-T-C is Benign according to our data. Variant chr11-116791110-T-C is described in ClinVar as Benign. ClinVar VariationId is 1297445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.978 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.162-43A>G		intron	N/A	NP_001358833.1	Q6Q788
	APOA5	NM_001166598.2		c.162-43A>G		intron	N/A	NP_001160070.1	A0A0B4RUS7
	APOA5	NM_052968.5		c.162-43A>G		intron	N/A	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.162-43A>G		intron	N/A	ENSP00000227665.4	Q6Q788
	APOA5	ENST00000433069.2	TSL:1	c.162-43A>G		intron	N/A	ENSP00000399701.2	Q6Q788
	APOA5	ENST00000673688.1		c.203A>G	p.Glu68Gly	missense	Exon 3 of 3	ENSP00000501141.1	A0A669KB69

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142139 AN: 152202 Hom.: 66601 Cov.: 33

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.922

GnomAD2 exomes AF: 0.894 AC: 167051 AN: 186868 AF XY: 0.893

Gnomad AFR exome AF: 0.989

Gnomad AMR exome AF: 0.833

Gnomad ASJ exome AF: 0.913

Gnomad EAS exome AF: 0.784

Gnomad FIN exome AF: 0.919

Gnomad NFE exome AF: 0.936

Gnomad OTH exome AF: 0.913

GnomAD4 exome AF: 0.924 AC: 1238710 AN: 1340582 Hom.: 573892 Cov.: 21 AF XY: 0.921 AC XY: 616835 AN XY: 669506

African (AFR) AF: 0.990 AC: 30768 AN: 31078

American (AMR) AF: 0.839 AC: 33044 AN: 39408

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 22931 AN: 25132

East Asian (EAS) AF: 0.752 AC: 28312 AN: 37636

South Asian (SAS) AF: 0.832 AC: 67613 AN: 81282

European-Finnish (FIN) AF: 0.919 AC: 36375 AN: 39576

Middle Eastern (MID) AF: 0.898 AC: 5000 AN: 5570

European-Non Finnish (NFE) AF: 0.940 AC: 962902 AN: 1024406

Other (OTH) AF: 0.916 AC: 51765 AN: 56494

GnomAD4 genome AF: 0.934 AC: 142244 AN: 152320 Hom.: 66650 Cov.: 33 AF XY: 0.930 AC XY: 69293 AN XY: 74486

African (AFR) AF: 0.986 AC: 40985 AN: 41576

American (AMR) AF: 0.891 AC: 13627 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3165 AN: 3472

East Asian (EAS) AF: 0.768 AC: 3971 AN: 5168

South Asian (SAS) AF: 0.827 AC: 3994 AN: 4832

European-Finnish (FIN) AF: 0.920 AC: 9760 AN: 10612

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.936 AC: 63687 AN: 68036

Other (OTH) AF: 0.917 AC: 1941 AN: 2116

Alfa AF: 0.943 Hom.: 27219

Bravo AF: 0.934

Asia WGS AF: 0.810 AC: 2819 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.72
PhyloP100		-0.54
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: rs2072560; hg19: chr11-116661826; COSMIC: COSV57065926; COSMIC: COSV57065926;