rs41338746

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.420

Publications

4 publications found

Variant links:

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]

APOA5 Gene-Disease associations (from GenCC):

hypertriglyceridemia 1
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
hyperlipoproteinemia type V
Inheritance: AD, SD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

APOA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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	Effect	Exon rank	MANE	Protein	UniProt
APOA5	NM_001371904.1 link	c.49+55G>T	intron_variant	Intron 1 of 2	ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2 link	c.49+55G>T	intron_variant	Intron 2 of 3		NP_001160070.1	Q6Q788A0A0B4RUS7
APOA5	NM_052968.5 link	c.49+55G>T	intron_variant	Intron 2 of 3		NP_443200.2	Q6Q788A0A0B4RUS7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOA5	ENST00000227665.9 link	c.49+55G>T	intron_variant	Intron 1 of 2	1	NM_001371904.1	ENSP00000227665.4	Q6Q788
APOA5	ENST00000433069.2 link	c.49+55G>T	intron_variant	Intron 2 of 3	1		ENSP00000399701.2	Q6Q788
APOA5	ENST00000673688.1 link	c.49+55G>T	intron_variant	Intron 1 of 2			ENSP00000501141.1	A0A669KB69
APOA5	ENST00000542499.5 link	c.49+55G>T	intron_variant	Intron 2 of 3	5		ENSP00000445002.1	Q6Q788

Frequencies

GnomAD3 genomes

AF:

0.0430

AC:

6537

AN:

152186

Hom.:

445

Cov.:

show subpopulations

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.:

AF XY:

0.00444

AC XY:

3224

AN XY:

726920

show subpopulations

African (AFR)

AF:

0.159

AC:

5304

AN:

33458

American (AMR)

AF:

0.00727

AC:

325

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.0168

AC:

440

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.000336

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.00971

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000459

AC:

510

AN:

1111656

Other (OTH)

AF:

0.00992

AC:

599

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

398

795

1193

1590

1988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0430

AC:

6549

AN:

152304

Hom.:

445

Cov.:

AF XY:

0.0418

AC XY:

3112

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.147

AC:

6111

AN:

41536

American (AMR)

AF:

0.0165

AC:

252

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000779

AC:

AN:

68026

Other (OTH)

AF:

0.0331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

263

526

790

1053

1316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0260

Hom.:

Bravo

AF:

0.0506

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 07, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.2

(source)

DANN

Benign

0.82

PhyloP100

-0.42

PromoterAI

-0.045

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over