NM_000039.3:c.200+33T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id is 1251605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116836968-A-G is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA1	NM_000039.3 link	c.200+33T>C		intron_variant	Intron 3 of 3	ENST00000236850.5	NP_000030.1	P02647A0A024R3E3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA1	ENST00000236850.5 link	c.200+33T>C		intron_variant	Intron 3 of 3	1	NM_000039.3	ENSP00000236850.3		P02647

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

GnomAD3 exomes

AF:

0.849

AC:

212034

AN:

249616

Hom.:

91128

AF XY:

0.845

AC XY:

114482

AN XY:

135410

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 SAS exome

AF:

0.697

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

Gnomad4 AFR exome

AF:

0.904

Gnomad4 AMR exome

AF:

0.801

Gnomad4 ASJ exome

AF:

0.862

Gnomad4 EAS exome

AF:

0.625

Gnomad4 SAS exome

AF:

0.699

Gnomad4 FIN exome

AF:

0.880

Gnomad4 NFE exome

AF:

0.924

Gnomad4 OTH exome

AF:

0.880

GnomAD4 genome

AF:

0.884

AC:

134632

AN:

152266

Hom.:

59864

Cov.:

AF XY:

0.876

AC XY:

65199

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.907

Gnomad4 AMR

AF:

0.820

Gnomad4 ASJ

AF:

0.859

Gnomad4 EAS

AF:

0.668

Gnomad4 SAS

AF:

0.684

Gnomad4 FIN

AF:

0.873

Gnomad4 NFE

AF:

0.918

Gnomad4 OTH

AF:

0.874

Alfa

AF:

0.909

Hom.:

66514

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

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.28

DANN

Benign

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over