11-116791863-C-T

Variant names:

• chr11-116791863-C-T
• rs651821
• NM_001371904.1:c.-3G>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.-3G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 1,614,018 control chromosomes in the GnomAD database, including 675,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60477 hom., cov: 34)
  • Exomes 𝑓: 0.92 (615172 hom.)
• Consequence: APOA5 NM_001371904.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.137

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=-0.85).
• BP6: Variant 11-116791863-C-T is Benign according to our data. Variant chr11-116791863-C-T is described in ClinVar as [Benign]. Clinvar id is 1284811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116791863-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA5	NM_001371904.1	c.-3G>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2	c.-3G>A		5_prime_UTR_variant	Exon 2 of 4		NP_001160070.1
APOA5	NM_052968.5	c.-3G>A		5_prime_UTR_variant	Exon 2 of 4		NP_443200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA5	ENST00000227665.9	c.-3G>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_001371904.1	ENSP00000227665.4
APOA5	ENST00000433069.2	c.-3G>A		5_prime_UTR_variant	Exon 2 of 4	1		ENSP00000399701.2
APOA5	ENST00000673688.1	c.-3G>A		5_prime_UTR_variant	Exon 1 of 3			ENSP00000501141.1
APOA5	ENST00000542499.5	c.-3G>A		5_prime_UTR_variant	Exon 2 of 4	5		ENSP00000445002.1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135380 AN: 152184 Hom.: 60460 Cov.: 34

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.884

GnomAD3 exomes AF: 0.879 AC: 220186 AN: 250512 Hom.: 97522 AF XY: 0.881 AC XY: 119421 AN XY: 135580

Gnomad AFR exome AF: 0.848

Gnomad AMR exome AF: 0.820

Gnomad ASJ exome AF: 0.899

Gnomad EAS exome AF: 0.715

Gnomad SAS exome AF: 0.818

Gnomad FIN exome AF: 0.918

Gnomad NFE exome AF: 0.934

Gnomad OTH exome AF: 0.901

GnomAD4 exome AF: 0.916 AC: 1338287 AN: 1461716 Hom.: 615172 Cov.: 57 AF XY: 0.913 AC XY: 663959 AN XY: 727154

Gnomad4 AFR exome AF: 0.842

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.898

Gnomad4 EAS exome AF: 0.679

Gnomad4 SAS exome AF: 0.819

Gnomad4 FIN exome AF: 0.918

Gnomad4 NFE exome AF: 0.939

Gnomad4 OTH exome AF: 0.901

GnomAD4 genome AF: 0.889 AC: 135451 AN: 152302 Hom.: 60477 Cov.: 34 AF XY: 0.886 AC XY: 66012 AN XY: 74482

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.864

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.920

Gnomad4 NFE AF: 0.934

Gnomad4 OTH AF: 0.879

Alfa AF: 0.922 Hom.: 139825

Bravo AF: 0.884

Asia WGS AF: 0.766 AC: 2665 AN: 3478

EpiCase AF: 0.928

EpiControl AF: 0.927

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 07, 2023

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.76

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: rs651821; hg19: chr11-116662579; COSMIC: COSV57065156; COSMIC: COSV57065156;