rs2274873

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005502.4(ABCA1):c.936C>T(p.Pro312Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 1,614,018 control chromosomes in the GnomAD database, including 7,922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 702 hom., cov: 32)

Exomes 𝑓: 0.097 ( 7220 hom. )

Consequence

ABCA1
NM_005502.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.18

Publications

39 publications found

Variant links:

Genes affected

ABCA1 (HGNC:29): (ATP binding cassette subfamily A member 1) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

ABCA1 Gene-Disease associations (from GenCC):

hypoalphalipoproteinemia, primary, 1
Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Tangier disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
apolipoprotein A-I deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ABCA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 9-104840397-G-A is Benign according to our data. Variant chr9-104840397-G-A is described in ClinVar as Benign. ClinVar VariationId is 364451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4 link	c.936C>T	p.Pro312Pro	synonymous_variant	Exon 9 of 50	ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8 link	c.936C>T	p.Pro312Pro	synonymous_variant	Exon 9 of 50	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1 link	c.936C>T	p.Pro312Pro	synonymous_variant	Exon 9 of 50			ENSP00000504612.1

Frequencies

GnomAD3 genomes

AF:

0.0921

AC:

14010

AN:

152044

Hom.:

703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0972

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.0578

Gnomad ASJ

AF:

0.0822

Gnomad EAS

AF:

0.0702

Gnomad SAS

AF:

0.0838

Gnomad FIN

AF:

0.0886

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0988

Gnomad OTH

AF:

0.0836

GnomAD2 exomes

AF:

0.0848

AC:

21313

AN:

251422

AF XY:

0.0865

show subpopulations

Gnomad AFR exome

AF:

0.0966

Gnomad AMR exome

AF:

0.0379

Gnomad ASJ exome

AF:

0.0864

Gnomad EAS exome

AF:

0.0671

Gnomad FIN exome

AF:

0.0819

Gnomad NFE exome

AF:

0.0993

Gnomad OTH exome

AF:

0.0844

GnomAD4 exome

AF:

0.0974

AC:

142332

AN:

1461856

Hom.:

7220

Cov.:

AF XY:

0.0974

AC XY:

70811

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.102

AC:

3427

AN:

33480

American (AMR)

AF:

0.0393

AC:

1759

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0858

AC:

2241

AN:

26134

East Asian (EAS)

AF:

0.0917

AC:

3642

AN:

39700

South Asian (SAS)

AF:

0.0857

AC:

7396

AN:

86254

European-Finnish (FIN)

AF:

0.0832

AC:

4445

AN:

53418

Middle Eastern (MID)

AF:

0.100

AC:

579

AN:

5768

European-Non Finnish (NFE)

AF:

0.102

AC:

113018

AN:

1111984

Other (OTH)

AF:

0.0964

AC:

5825

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

8186

16371

24557

32742

40928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4124

8248

12372

16496

20620

<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:

0.0922

AC:

14023

AN:

152162

Hom.:

702

Cov.:

AF XY:

0.0900

AC XY:

6697

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0973

AC:

4038

AN:

41502

American (AMR)

AF:

0.0578

AC:

883

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0822

AC:

285

AN:

3466

East Asian (EAS)

AF:

0.0698

AC:

361

AN:

5170

South Asian (SAS)

AF:

0.0830

AC:

400

AN:

4818

European-Finnish (FIN)

AF:

0.0886

AC:

939

AN:

10594

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0988

AC:

6721

AN:

68000

Other (OTH)

AF:

0.0851

AC:

180

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

647

1295

1942

2590

3237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0955

Hom.:

2508

Bravo

AF:

0.0893

Asia WGS

AF:

0.105

AC:

364

AN:

3478

EpiCase

AF:

0.103

EpiControl

AF:

0.0997

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 04, 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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ABCA1-related disorder

Benign:1

Jul 08, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Cardiovascular phenotype

Benign:1

Dec 11, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Tangier disease

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hypoalphalipoproteinemia, primary, 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

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

-0.38

CADD

Benign

0.35

(source)

DANN

Benign

0.63

PhyloP100

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=84/16

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