11-116790097-G-A

Variant names:

• chr11-116790097-G-A
• rs619054
• NM_001371904.1:c.*31C>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.*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
• Publications: 39 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=-0.78).
• BP6: Variant 11-116790097-G-A is Benign according to our data. Variant chr11-116790097-G-A is described in ClinVar as Benign. ClinVar VariationId is 1293389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA5	NM_001371904.1	MANE Select	c.*31C>T		3_prime_UTR	Exon 3 of 3	NP_001358833.1
	APOA5	NM_001166598.2		c.*31C>T		3_prime_UTR	Exon 4 of 4	NP_001160070.1
	APOA5	NM_052968.5		c.*31C>T		3_prime_UTR	Exon 4 of 4	NP_443200.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA5	ENST00000227665.9	TSL:1 MANE Select	c.*31C>T		3_prime_UTR	Exon 3 of 3	ENSP00000227665.4
	APOA5	ENST00000433069.2	TSL:1	c.*31C>T		3_prime_UTR	Exon 4 of 4	ENSP00000399701.2
	APOA5	ENST00000673688.1		c.*31C>T		3_prime_UTR	Exon 3 of 3	ENSP00000501141.1

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

GnomAD2 exomes AF: 0.189 AC: 45691 AN: 241740 AF XY: 0.194

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 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

African (AFR) AF: 0.114 AC: 3802 AN: 33280

American (AMR) AF: 0.134 AC: 5908 AN: 44000

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 6698 AN: 25982

East Asian (EAS) AF: 0.000939 AC: 37 AN: 39422

South Asian (SAS) AF: 0.146 AC: 12430 AN: 85376

European-Finnish (FIN) AF: 0.223 AC: 11834 AN: 53106

Middle Eastern (MID) AF: 0.247 AC: 1422 AN: 5746

European-Non Finnish (NFE) AF: 0.246 AC: 272118 AN: 1105254

Other (OTH) AF: 0.217 AC: 12988 AN: 59990

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

African (AFR) AF: 0.118 AC: 4883 AN: 41550

American (AMR) AF: 0.171 AC: 2623 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 875 AN: 3470

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5182

South Asian (SAS) AF: 0.131 AC: 632 AN: 4832

European-Finnish (FIN) AF: 0.222 AC: 2351 AN: 10586

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17042 AN: 67990

Other (OTH) AF: 0.202 AC: 427 AN: 2112

Alfa AF: 0.234 Hom.: 6228

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.75
PhyloP100		-0.41
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: rs619054; hg19: chr11-116660813;