9-104903470-C-T

Variant names:

Variant summary

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

The NM_005502.4(ABCA1):c.66+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 870,922 control chromosomes in the GnomAD database, including 8,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1346 hom., cov: 32)

Exomes 𝑓: 0.14 ( 7591 hom. )

Consequence

ABCA1
NM_005502.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.654

Publications

12 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 9-104903470-C-T is Benign according to our data. Variant chr9-104903470-C-T is described in CliVar as Benign. Clinvar id is 1221279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104903470-C-T is described in CliVar as Benign. Clinvar id is 1221279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104903470-C-T is described in CliVar as Benign. Clinvar id is 1221279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104903470-C-T is described in CliVar as Benign. Clinvar id is 1221279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104903470-C-T is described in CliVar as Benign. Clinvar id is 1221279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4 link	c.66+144G>A		intron_variant	Intron 2 of 49	ENST00000374736.8	NP_005493.2	O95477B7XCW9B2RUU2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCA1	ENST00000374736.8 link	c.66+144G>A	intron_variant	Intron 2 of 49	1	NM_005502.4	ENSP00000363868.3	O95477
ABCA1	ENST00000678995.1 link	c.66+144G>A	intron_variant	Intron 2 of 49			ENSP00000504612.1	A0A7I2V5U0
ABCA1	ENST00000423487.6 link	c.66+144G>A	intron_variant	Intron 2 of 7	2		ENSP00000416623.2	B1AMI2
ABCA1	ENST00000374733.1 link	c.-114-14275G>A	intron_variant	Intron 1 of 4	2		ENSP00000363865.1	B1AMI1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17667

AN:

152086

Hom.:

1348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0284

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.0824

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.124

GnomAD4 exome

AF:

0.138

AC:

98914

AN:

718718

Hom.:

7591

AF XY:

0.137

AC XY:

51857

AN XY:

378182

show subpopulations

African (AFR)

AF:

0.0254

AC:

474

AN:

18640

American (AMR)

AF:

0.269

AC:

9287

AN:

34550

Ashkenazi Jewish (ASJ)

AF:

0.0811

AC:

1670

AN:

20594

East Asian (EAS)

AF:

0.136

AC:

4436

AN:

32706

South Asian (SAS)

AF:

0.144

AC:

9264

AN:

64456

European-Finnish (FIN)

AF:

0.145

AC:

6561

AN:

45152

Middle Eastern (MID)

AF:

0.0867

AC:

378

AN:

4358

European-Non Finnish (NFE)

AF:

0.135

AC:

62275

AN:

462350

Other (OTH)

AF:

0.127

AC:

4569

AN:

35912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

4670

9340

14010

18680

23350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1236

2472

3708

4944

6180

<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:

0.116

AC:

17669

AN:

152204

Hom.:

1346

Cov.:

AF XY:

0.120

AC XY:

8933

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0283

AC:

1175

AN:

41530

American (AMR)

AF:

0.228

AC:

3486

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0824

AC:

286

AN:

3470

East Asian (EAS)

AF:

0.169

AC:

875

AN:

5176

South Asian (SAS)

AF:

0.145

AC:

700

AN:

4824

European-Finnish (FIN)

AF:

0.146

AC:

1549

AN:

10602

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9271

AN:

67994

Other (OTH)

AF:

0.123

AC:

259

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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

196

392

588

784

980

<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:

0.130

Hom.:

2695

Bravo

AF:

0.117

Asia WGS

AF:

0.165

AC:

576

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 23, 2018

GeneDx

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

-0.77

CADD

Benign

7.0

(source)

DANN

Benign

0.68

PhyloP100

0.65

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over