Variant 9-104802185-C-G 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.4593-26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 1,595,932 control chromosomes in the GnomAD database, including 5,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 431 hom., cov: 33)

Exomes 𝑓: 0.080 ( 5355 hom. )

Consequence

ABCA1
NM_005502.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.157

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=-0.61).

BP6

Variant 9-104802185-C-G is Benign according to our data. Variant chr9-104802185-C-G is described in ClinVar as [Benign]. Clinvar id is 1297172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104802185-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 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.4593-26G>C		intron_variant		ENST00000374736.8	NP_005493.2	O95477B7XCW9B2RUU2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8 linkuse as main transcript	c.4593-26G>C		intron_variant		1	NM_005502.4	ENSP00000363868.3		O95477
ABCA1	ENST00000678995.1 linkuse as main transcript	c.4599-26G>C		intron_variant				ENSP00000504612.1		A0A7I2V5U0

Frequencies

GnomAD3 genomes

AF:

0.0666

AC:

10122

AN:

152084

Hom.:

429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0393

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0552

Gnomad ASJ

AF:

0.0404

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.0987

Gnomad FIN

AF:

0.0445

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0749

Gnomad OTH

AF:

0.0731

GnomAD3 exomes

AF:

0.0785

AC:

19691

AN:

250934

Hom.:

1123

AF XY:

0.0813

AC XY:

11025

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.0408

Gnomad AMR exome

AF:

0.0356

Gnomad ASJ exome

AF:

0.0379

Gnomad EAS exome

AF:

0.234

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.0462

Gnomad NFE exome

AF:

0.0759

Gnomad OTH exome

AF:

0.0673

GnomAD4 exome

AF:

0.0801

AC:

115648

AN:

1443730

Hom.:

5355

Cov.:

AF XY:

0.0808

AC XY:

58160

AN XY:

719680

show subpopulations

Gnomad4 AFR exome

AF:

0.0399

Gnomad4 AMR exome

AF:

0.0360

Gnomad4 ASJ exome

AF:

0.0387

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.0994

Gnomad4 FIN exome

AF:

0.0474

Gnomad4 NFE exome

AF:

0.0793

Gnomad4 OTH exome

AF:

0.0811

GnomAD4 genome

AF:

0.0666

AC:

10131

AN:

152202

Hom.:

431

Cov.:

AF XY:

0.0652

AC XY:

4853

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0393

Gnomad4 AMR

AF:

0.0551

Gnomad4 ASJ

AF:

0.0404

Gnomad4 EAS

AF:

0.228

Gnomad4 SAS

AF:

0.0996

Gnomad4 FIN

AF:

0.0445

Gnomad4 NFE

AF:

0.0750

Gnomad4 OTH

AF:

0.0743

Alfa

AF:

0.0422

Hom.:

Bravo

AF:

0.0659

Asia WGS

AF:

0.158

AC:

547

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	Nov 07, 2018	This variant is associated with the following publications: (PMID: 17510949) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.70

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