Variant 9-104830901-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005502.4(ABCA1):c.1892+24T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,612,060 control chromosomes in the GnomAD database, including 96,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 18514 hom., cov: 29)

Exomes 𝑓: 0.30 ( 77945 hom. )

Consequence

ABCA1
NM_005502.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.917

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 links:

ABCA1 (HGNC:):

ABCA1 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=-0.85).

BP6

Variant 9-104830901-A-T is Benign according to our data. Variant chr9-104830901-A-T is described in ClinVar as [Benign]. Clinvar id is 1232269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104830901-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA1	NM_005502.4 linkuse as main transcript	c.1892+24T>A		intron_variant		ENST00000374736.8	NP_005493.2	O95477B7XCW9B2RUU2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ABCA1	ENST00000374736.8 linkuse as main transcript	c.1892+24T>A	intron_variant	1	NM_005502.4	ENSP00000363868.3	O95477
ABCA1	ENST00000678995.1 linkuse as main transcript	c.1892+24T>A	intron_variant			ENSP00000504612.1	A0A7I2V5U0
ABCA1	ENST00000494467.1 linkuse as main transcript	n.65+24T>A	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66176

AN:

151468

Hom.:

18454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.767

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.795

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.439

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.428

GnomAD3 exomes

AF:

0.363

AC:

91232

AN:

251440

Hom.:

20809

AF XY:

0.348

AC XY:

47261

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.773

Gnomad AMR exome

AF:

0.406

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.808

Gnomad SAS exome

AF:

0.302

Gnomad FIN exome

AF:

0.206

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.348

GnomAD4 exome

AF:

0.302

AC:

441259

AN:

1460474

Hom.:

77945

Cov.:

AF XY:

0.301

AC XY:

218660

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.787

Gnomad4 AMR exome

AF:

0.407

Gnomad4 ASJ exome

AF:

0.330

Gnomad4 EAS exome

AF:

0.800

Gnomad4 SAS exome

AF:

0.306

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.266

Gnomad4 OTH exome

AF:

0.347

GnomAD4 genome

AF:

0.437

AC:

66295

AN:

151586

Hom.:

18514

Cov.:

AF XY:

0.435

AC XY:

32180

AN XY:

74046

show subpopulations

Gnomad4 AFR

AF:

0.768

Gnomad4 AMR

AF:

0.404

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.794

Gnomad4 SAS

AF:

0.317

Gnomad4 FIN

AF:

0.214

Gnomad4 NFE

AF:

0.266

Gnomad4 OTH

AF:

0.434

Alfa

AF:

0.333

Hom.:

1911

Bravo

AF:

0.471

Asia WGS

AF:

0.584

AC:

2029

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.3

DANN

Benign

0.66

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