11-116836968-A-G

Variant names:

Variant summary

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

The NM_000039.3(APOA1):c.200+33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 1,612,302 control chromosomes in the GnomAD database, including 647,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59864 hom., cov: 33)

Exomes 𝑓: 0.89 ( 587136 hom. )

Consequence

APOA1
NM_000039.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.65

Publications

42 publications found

Variant links:

Genes affected

APOA1 (HGNC:600): (apolipoprotein A1) This gene encodes apolipoprotein A-I, which is the major protein component of high density lipoprotein (HDL) in plasma. The encoded preproprotein is proteolytically processed to generate the mature protein, which promotes cholesterol efflux from tissues to the liver for excretion, and is a cofactor for lecithin cholesterolacyltransferase (LCAT), an enzyme responsible for the formation of most plasma cholesteryl esters. This gene is closely linked with two other apolipoprotein genes on chromosome 11. Defects in this gene are associated with HDL deficiencies, including Tangier disease, and with systemic non-neuropathic amyloidosis. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein. [provided by RefSeq, Dec 2015]

APOA1 links:

APOA1-AS (HGNC:40079): (APOA1 antisense RNA)

APOA1-AS 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=-0.9).

BP6

Variant 11-116836968-A-G is Benign according to our data. Variant chr11-116836968-A-G is described in ClinVar as Benign. ClinVar VariationId is 1251605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000039.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
APOA1	NM_000039.3	MANE Select	c.200+33T>C	intron	N/A	NP_000030.1
APOA1	NM_001318017.2		c.200+33T>C	intron	N/A	NP_001304946.1
APOA1	NM_001318018.2		c.200+33T>C	intron	N/A	NP_001304947.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
APOA1	ENST00000236850.5	TSL:1 MANE Select	c.200+33T>C	intron	N/A	ENSP00000236850.3
APOA1	ENST00000375323.5	TSL:1	c.200+33T>C	intron	N/A	ENSP00000364472.1
APOA1	ENST00000359492.6	TSL:2	c.200+33T>C	intron	N/A	ENSP00000352471.2

Frequencies

GnomAD3 genomes

AF:

0.884

AC:

134544

AN:

152148

Hom.:

59831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.907

Gnomad AMI

AF:

0.970

Gnomad AMR

AF:

0.820

Gnomad ASJ

AF:

0.859

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.684

Gnomad FIN

AF:

0.873

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.918

Gnomad OTH

AF:

0.878

GnomAD2 exomes

AF:

0.849

AC:

212034

AN:

249616

AF XY:

0.845

show subpopulations

Gnomad AFR exome

AF:

0.900

Gnomad AMR exome

AF:

0.798

Gnomad ASJ exome

AF:

0.861

Gnomad EAS exome

AF:

0.689

Gnomad FIN exome

AF:

0.879

Gnomad NFE exome

AF:

0.918

Gnomad OTH exome

AF:

0.870

GnomAD4 exome

AF:

0.893

AC:

1304481

AN:

1460036

Hom.:

587136

Cov.:

AF XY:

0.887

AC XY:

644609

AN XY:

726430

show subpopulations

African (AFR)

AF:

0.904

AC:

30254

AN:

33450

American (AMR)

AF:

0.801

AC:

35834

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.862

AC:

22528

AN:

26130

East Asian (EAS)

AF:

0.625

AC:

24810

AN:

39688

South Asian (SAS)

AF:

0.699

AC:

60255

AN:

86216

European-Finnish (FIN)

AF:

0.880

AC:

46250

AN:

52576

Middle Eastern (MID)

AF:

0.855

AC:

4922

AN:

5758

European-Non Finnish (NFE)

AF:

0.924

AC:

1026523

AN:

1111146

Other (OTH)

AF:

0.880

AC:

53105

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

7145

14290

21435

28580

35725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21444

42888

64332

85776

107220

<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:

0.884

AC:

134632

AN:

152266

Hom.:

59864

Cov.:

AF XY:

0.876

AC XY:

65199

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.907

AC:

37675

AN:

41546

American (AMR)

AF:

0.820

AC:

12534

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.859

AC:

2982

AN:

3472

East Asian (EAS)

AF:

0.668

AC:

3449

AN:

5162

South Asian (SAS)

AF:

0.684

AC:

3299

AN:

4824

European-Finnish (FIN)

AF:

0.873

AC:

9266

AN:

10616

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.918

AC:

62446

AN:

68034

Other (OTH)

AF:

0.874

AC:

1845

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

777

1555

2332

3110

3887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<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:

0.906

Hom.:

105815

Bravo

AF:

0.888

Asia WGS

AF:

0.681

AC:

2374

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

Aug 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hypoalphalipoproteinemia, primary, 2, intermediate

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hypoalphalipoproteinemia, primary, 2

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Familial visceral amyloidosis, Ostertag type

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.28

(source)

DANN

Benign

0.35

PhyloP100

-4.7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over