Variant 9-104883196-G-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 ENST00000374736.8(ABCA1):c.303-39C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,530,888 control chromosomes in the GnomAD database, including 1,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 923 hom., cov: 33)

Exomes 𝑓: 0.011 ( 925 hom. )

Consequence

ABCA1
ENST00000374736.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.27

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=-0.63).

BP6

Variant 9-104883196-G-T is Benign according to our data. Variant chr9-104883196-G-T is described in ClinVar as [Benign]. Clinvar id is 1248989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 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.303-39C>A		intron_variant		ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ABCA1	ENST00000374736.8 linkuse as main transcript	c.303-39C>A	intron_variant	1	NM_005502.4	ENSP00000363868	P1
ABCA1	ENST00000374733.1 linkuse as main transcript	c.123-39C>A	intron_variant	2		ENSP00000363865
ABCA1	ENST00000423487.6 linkuse as main transcript	c.303-39C>A	intron_variant	2		ENSP00000416623
ABCA1	ENST00000678995.1 linkuse as main transcript	c.303-39C>A	intron_variant			ENSP00000504612

Frequencies

GnomAD3 genomes

AF:

0.0642

AC:

9762

AN:

152142

Hom.:

919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0267

Gnomad ASJ

AF:

0.0769

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.00434

Gnomad OTH

AF:

0.0542

GnomAD3 exomes

AF:

0.0222

AC:

5571

AN:

251306

Hom.:

421

AF XY:

0.0180

AC XY:

2444

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.0175

Gnomad ASJ exome

AF:

0.0700

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00353

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00481

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0107

AC:

14786

AN:

1378628

Hom.:

925

Cov.:

AF XY:

0.00999

AC XY:

6899

AN XY:

690650

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.0182

Gnomad4 ASJ exome

AF:

0.0724

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00327

Gnomad4 FIN exome

AF:

0.000338

Gnomad4 NFE exome

AF:

0.00309

Gnomad4 OTH exome

AF:

0.0237

GnomAD4 genome

AF:

0.0642

AC:

9769

AN:

152260

Hom.:

923

Cov.:

AF XY:

0.0609

AC XY:

4534

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.0266

Gnomad4 ASJ

AF:

0.0769

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00434

Gnomad4 OTH

AF:

0.0536

Alfa

AF:

0.0405

Hom.:

Bravo

AF:

0.0738

Asia WGS

AF:

0.0170

AC:

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	Oct 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.7

DANN

Benign

0.73

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