11-116790116-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001371904.1(APOA5):c.*12C>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 0.00151 in 1,613,238 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0015 (2 hom.)
• Consequence: APOA5 NM_001371904.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.970

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-116790116-G-A is Benign according to our data. Variant chr11-116790116-G-A is described in ClinVar as [Benign]. Clinvar id is 2581547.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-116790116-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00109 (166/152366) while in subpopulation NFE AF= 0.00162 (110/68030). AF 95% confidence interval is 0.00137. There are 0 homozygotes in gnomad4. There are 73 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOA5	NM_001371904.1	c.*12C>T		3_prime_UTR_variant	3/3	ENST00000227665.9
APOA5	NM_001166598.2	c.*12C>T		3_prime_UTR_variant	4/4
APOA5	NM_052968.5	c.*12C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOA5	ENST00000227665.9	c.*12C>T		3_prime_UTR_variant	3/3	1	NM_001371904.1	P1
APOA5	ENST00000433069.2	c.*12C>T		3_prime_UTR_variant	4/4	1		P1
APOA5	ENST00000542499.5	c.*12C>T		3_prime_UTR_variant	4/4	5		P1
APOA5	ENST00000673688.1	c.*12C>T		3_prime_UTR_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 166 AN: 152248 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00156 AC: 390 AN: 249574 Hom.: 1 AF XY: 0.00162 AC XY: 219 AN XY: 135080

Gnomad AFR exome AF: 0.000249

Gnomad AMR exome AF: 0.000494

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00138

Gnomad FIN exome AF: 0.00293

Gnomad NFE exome AF: 0.00231

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.00155 AC: 2262 AN: 1460872 Hom.: 2 Cov.: 33 AF XY: 0.00150 AC XY: 1093 AN XY: 726698

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.000493

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00128

Gnomad4 FIN exome AF: 0.00223

Gnomad4 NFE exome AF: 0.00173

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152366 Hom.: 0 Cov.: 34 AF XY: 0.000980 AC XY: 73 AN XY: 74512

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.00162

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00126 Hom.: 0

Bravo AF: 0.000808

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.95
Dann	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs185060854; hg19: chr11-116660832;