Variant rs2254884 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.3241+118T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,418,434 control chromosomes in the GnomAD database, including 63,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5371 hom., cov: 32)

Exomes 𝑓: 0.30 ( 58108 hom. )

Consequence

ABCA1
NM_005502.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.279

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:

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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=-0.93).

BP6

Variant 9-104819468-A-C is Benign according to our data. Variant chr9-104819468-A-C is described in ClinVar as [Benign]. Clinvar id is 1263599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104819468-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 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.3241+118T>G		intron_variant		ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8 linkuse as main transcript	c.3241+118T>G		intron_variant		1	NM_005502.4	ENSP00000363868	P1
ABCA1	ENST00000678995.1 linkuse as main transcript	c.3241+118T>G		intron_variant				ENSP00000504612

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37086

AN:

152034

Hom.:

5372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.362

Gnomad AMR

AF:

0.260

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.548

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.275

GnomAD4 exome

AF:

0.297

AC:

376009

AN:

1266282

Hom.:

58108

AF XY:

0.297

AC XY:

189953

AN XY:

639538

show subpopulations

Gnomad4 AFR exome

AF:

0.0990

Gnomad4 AMR exome

AF:

0.275

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.528

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.300

Gnomad4 OTH exome

AF:

0.296

GnomAD4 genome

AF:

0.244

AC:

37092

AN:

152152

Hom.:

5371

Cov.:

AF XY:

0.243

AC XY:

18074

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.260

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.548

Gnomad4 SAS

AF:

0.267

Gnomad4 FIN

AF:

0.240

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.280

Hom.:

8159

Bravo

AF:

0.242

Asia WGS

AF:

0.383

AC:

1334

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

-0.93

CADD

Benign

1.5

DANN

Benign

0.64

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