dbSNP rs5069: APOA1:c.-151C>T (chr11-116837538-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001318017.2(APOA1):c.-31C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 950,756 control chromosomes in the GnomAD database, including 3,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1849 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1369 hom. )

Consequence

APOA1
NM_001318017.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.920

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-116837538-G-A is Benign according to our data. Variant chr11-116837538-G-A is described in ClinVar as [Benign]. Clinvar id is 1239868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116837538-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA1	NM_000039.3 link	c.-21+67C>T		intron_variant	Intron 1 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.-21+67C>T		intron_variant	Intron 1 of 3	1	NM_000039.3	ENSP00000236850.3		P02647

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

16021

AN:

152084

Hom.:

1849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0507

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0465

Gnomad SAS

AF:

0.0465

Gnomad FIN

AF:

0.0165

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0334

Gnomad OTH

AF:

0.0766

GnomAD4 exome

AF:

0.0393

AC:

31355

AN:

798554

Hom.:

1369

Cov.:

AF XY:

0.0383

AC XY:

15621

AN XY:

408216

show subpopulations

Gnomad4 AFR exome

AF:

0.296

Gnomad4 AMR exome

AF:

0.0333

Gnomad4 ASJ exome

AF:

0.0260

Gnomad4 EAS exome

AF:

0.0397

Gnomad4 SAS exome

AF:

0.0454

Gnomad4 FIN exome

AF:

0.0198

Gnomad4 NFE exome

AF:

0.0314

Gnomad4 OTH exome

AF:

0.0476

GnomAD4 genome

AF:

0.105

AC:

16029

AN:

152202

Hom.:

1849

Cov.:

AF XY:

0.103

AC XY:

7699

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.292

Gnomad4 AMR

AF:

0.0506

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0464

Gnomad4 SAS

AF:

0.0463

Gnomad4 FIN

AF:

0.0165

Gnomad4 NFE

AF:

0.0334

Gnomad4 OTH

AF:

0.0753

Alfa

AF:

0.0781

Hom.:

136

Bravo

AF:

0.117

Asia WGS

AF:

0.0580

AC:

200

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

- -

Sep 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28924542, 8647374) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.45

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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