11-116789956-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001371904.1(APOA5):c.*172C>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 0.00211 in 681,238 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (16 hom., cov: 33)
  • Exomes 𝑓: 0.00086 (3 hom.)
• Consequence: APOA5 NM_001371904.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.447

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-116789956-G-A is Benign according to our data. Variant chr11-116789956-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1206592.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-116789956-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00645 (982/152324) while in subpopulation AFR AF= 0.0222 (921/41570). AF 95% confidence interval is 0.021. There are 16 homozygotes in gnomad4. There are 434 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOA5	NM_001371904.1	c.*172C>T		3_prime_UTR_variant	3/3	ENST00000227665.9
APOA5	NM_001166598.2	c.*172C>T		3_prime_UTR_variant	4/4
APOA5	NM_052968.5	c.*172C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOA5	ENST00000227665.9	c.*172C>T		3_prime_UTR_variant	3/3	1	NM_001371904.1	P1
APOA5	ENST00000433069.2	c.*172C>T		3_prime_UTR_variant	4/4	1		P1
APOA5	ENST00000542499.5	c.*172C>T		3_prime_UTR_variant	4/4	5		P1

Frequencies

GnomAD3 genomes AF: 0.00648 AC: 986 AN: 152206 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000858 AC: 454 AN: 528914 Hom.: 3 Cov.: 6 AF XY: 0.000688 AC XY: 192 AN XY: 278894

Gnomad4 AFR exome AF: 0.0208

Gnomad4 AMR exome AF: 0.00299

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000523

Gnomad4 OTH exome AF: 0.00201

GnomAD4 genome AF: 0.00645 AC: 982 AN: 152324 Hom.: 16 Cov.: 33 AF XY: 0.00583 AC XY: 434 AN XY: 74482

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00303 Hom.: 2

Bravo AF: 0.00739

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 08, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.1
Dann	Benign	0.63
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: rs114627122; hg19: chr11-116660672;