11-116790097-G-A

Position:

• chr11-116790097-G-A

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.*31C>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 0.222 in 1,604,378 control chromosomes in the GnomAD database, including 42,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3246 hom., cov: 33)
  • Exomes 𝑓: 0.23 (39049 hom.)
• Consequence: APOA5 NM_001371904.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.411

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=-0.78).
• BP6: Variant 11-116790097-G-A is Benign according to our data. Variant chr11-116790097-G-A is described in ClinVar as [Benign]. Clinvar id is 1293389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116790097-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA5	NM_001371904.1	c.*31C>T		3_prime_UTR_variant	3/3	ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2	c.*31C>T		3_prime_UTR_variant	4/4		NP_001160070.1
APOA5	NM_052968.5	c.*31C>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.*31C>T		3_prime_UTR_variant	3/3	1	NM_001371904.1	ENSP00000227665	P1
APOA5	ENST00000433069.2	c.*31C>T		3_prime_UTR_variant	4/4	1		ENSP00000399701	P1
APOA5	ENST00000542499.5	c.*31C>T		3_prime_UTR_variant	4/4	5		ENSP00000445002	P1
APOA5	ENST00000673688.1	c.*31C>T		3_prime_UTR_variant	3/3			ENSP00000501141

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29131 AN: 152104 Hom.: 3240 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.204

GnomAD3 exomes AF: 0.189 AC: 45691 AN: 241740 Hom.: 4918 AF XY: 0.194 AC XY: 25371 AN XY: 130916

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.00151

Gnomad SAS exome AF: 0.144

Gnomad FIN exome AF: 0.219

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.225 AC: 327237 AN: 1452156 Hom.: 39049 Cov.: 32 AF XY: 0.225 AC XY: 162544 AN XY: 722306

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.000939

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.192 AC: 29162 AN: 152222 Hom.: 3246 Cov.: 33 AF XY: 0.189 AC XY: 14035 AN XY: 74436

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.202

Alfa AF: 0.241 Hom.: 4174

Bravo AF: 0.182

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Sep 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.75

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: rs619054; hg19: chr11-116660813;