dbSNP rs7116797: APOA1:c.201-211T>C (chr11-116836622-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000039.3(APOA1):c.201-211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,208 control chromosomes in the GnomAD database, including 45,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.76 ( 45366 hom., cov: 34)

Consequence

APOA1
NM_000039.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.226

Publications

17 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-116836622-A-G is Benign according to our data. Variant chr11-116836622-A-G is described in ClinVar as Benign. ClinVar VariationId is 1272681.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.878 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	UniProt
APOA1	NM_000039.3	MANE Select	c.201-211T>C	intron	N/A	NP_000030.1	A0A024R3E3
APOA1	NM_001318017.2		c.201-211T>C	intron	N/A	NP_001304946.1	A0A024R3E3
APOA1	NM_001318018.2		c.201-211T>C	intron	N/A	NP_001304947.1	P02647

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOA1	ENST00000236850.5	TSL:1 MANE Select	c.201-211T>C	intron	N/A	ENSP00000236850.3	P02647
APOA1	ENST00000375323.5	TSL:1	c.201-211T>C	intron	N/A	ENSP00000364472.1	P02647
APOA1	ENST00000855312.1		c.201-178T>C	intron	N/A	ENSP00000525371.1

Frequencies

GnomAD3 genomes

AF:

0.757

AC:

115172

AN:

152090

Hom.:

45349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.965

Gnomad AMR

AF:

0.764

Gnomad ASJ

AF:

0.834

Gnomad EAS

AF:

0.620

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.857

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.884

Gnomad OTH

AF:

0.790

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.757

AC:

115240

AN:

152208

Hom.:

45366

Cov.:

AF XY:

0.751

AC XY:

55894

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.540

AC:

22398

AN:

41502

American (AMR)

AF:

0.764

AC:

11684

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.834

AC:

2897

AN:

3472

East Asian (EAS)

AF:

0.621

AC:

3201

AN:

5158

South Asian (SAS)

AF:

0.640

AC:

3087

AN:

4826

European-Finnish (FIN)

AF:

0.857

AC:

9093

AN:

10612

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.884

AC:

60096

AN:

68018

Other (OTH)

AF:

0.787

AC:

1662

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1327

2654

3980

5307

6634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.775

Hom.:

6708

Bravo

AF:

0.747

Asia WGS

AF:

0.619

AC:

2158

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

8.4

(source)

DANN

Benign

0.70

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over