11-116789838-C-CCT

Position:

• chr11-116789838-C-CCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001371904.1(APOA5):​c.*289_*290insAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 510,500 control chromosomes in the GnomAD database, including 1,076 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (349 hom., cov: 32)
  • Exomes 𝑓: 0.042 (727 hom.)
• Consequence: APOA5 NM_001371904.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.265

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.

• BP6: Variant 11-116789838-C-CCT is Benign according to our data. Variant chr11-116789838-C-CCT is described in ClinVar as [Benign]. Clinvar id is 1227731.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA5	NM_001371904.1	c.*289_*290insAG		3_prime_UTR_variant	3/3	ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2	c.*289_*290insAG		3_prime_UTR_variant	4/4		NP_001160070.1
APOA5	NM_052968.5	c.*289_*290insAG		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.*289_*290insAG		3_prime_UTR_variant	3/3	1	NM_001371904.1	ENSP00000227665	P1
APOA5	ENST00000542499.5	c.*289_*290insAG		3_prime_UTR_variant	4/4	5		ENSP00000445002	P1

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8413 AN: 152158 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0549

GnomAD4 exome AF: 0.0421 AC: 15092 AN: 358224 Hom.: 727 Cov.: 0 AF XY: 0.0429 AC XY: 8082 AN XY: 188318

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0474

Gnomad4 ASJ exome AF: 0.0384

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.0614

Gnomad4 FIN exome AF: 0.0439

Gnomad4 NFE exome AF: 0.0195

Gnomad4 OTH exome AF: 0.0415

GnomAD4 genome AF: 0.0554 AC: 8429 AN: 152276 Hom.: 349 Cov.: 32 AF XY: 0.0586 AC XY: 4366 AN XY: 74474

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0627

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.0480

Gnomad4 NFE AF: 0.0217

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0421 Hom.: 27

Bravo AF: 0.0559

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 25, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs45596738; hg19: chr11-116660554;