rs41338746

Positions:

• chr11-116791757-C-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.49+55G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00856 in 1,613,600 control chromosomes in the GnomAD database, including 873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (445 hom., cov: 34)
  • Exomes 𝑓: 0.0050 (428 hom.)
• Consequence: APOA5 NM_001371904.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.420

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=-0.83).
• BP6: Variant 11-116791757-C-A is Benign according to our data. Variant chr11-116791757-C-A is described in ClinVar as [Benign]. Clinvar id is 1252218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA5	NM_001371904.1	c.49+55G>T		intron_variant		ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2	c.49+55G>T		intron_variant			NP_001160070.1
APOA5	NM_052968.5	c.49+55G>T		intron_variant			NP_443200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOA5	ENST00000227665.9	c.49+55G>T		intron_variant		1	NM_001371904.1	ENSP00000227665	P1
APOA5	ENST00000433069.2	c.49+55G>T		intron_variant		1		ENSP00000399701	P1
APOA5	ENST00000542499.5	c.49+55G>T		intron_variant		5		ENSP00000445002	P1
APOA5	ENST00000673688.1	c.49+55G>T		intron_variant				ENSP00000501141

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6537 AN: 152186 Hom.: 445 Cov.: 34

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.00497 AC: 7263 AN: 1461296 Hom.: 428 Cov.: 33 AF XY: 0.00444 AC XY: 3224 AN XY: 726920

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.00727

Gnomad4 ASJ exome AF: 0.0168

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000459

Gnomad4 OTH exome AF: 0.00992

GnomAD4 genome AF: 0.0430 AC: 6549 AN: 152304 Hom.: 445 Cov.: 34 AF XY: 0.0418 AC XY: 3112 AN XY: 74482

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0260 Hom.: 35

Bravo AF: 0.0506

Asia WGS AF: 0.00722 AC: 25 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	Apr 07, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.82
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: rs41338746; hg19: chr11-116662473; COSMIC: COSV57064895; COSMIC: COSV57064895;