Variant rs536009 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_172232.4(ABCA5):c.2494G>T(p.Ala832Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 1,607,574 control chromosomes in the GnomAD database, including 581,032 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.79 ( 48729 hom., cov: 31)

Exomes 𝑓: 0.85 ( 532303 hom. )

Consequence

ABCA5
NM_172232.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.321

Variant links:

Genes affected

ABCA5 (HGNC:35): (ATP binding cassette subfamily A member 5) 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, and White). This encoded protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This gene is clustered among 4 other ABC1 family members on 17q24, but neither the substrate nor the function of this gene is known. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

ABCA5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1026686E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA5	NM_172232.4 link	c.2494G>T	p.Ala832Ser	missense_variant	19/39	ENST00000392676.8	NP_758424.1	Q8WWZ7-1
ABCA5	NM_018672.5 link	c.2494G>T	p.Ala832Ser	missense_variant	18/38		NP_061142.2	Q8WWZ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA5	ENST00000392676.8 link	c.2494G>T	p.Ala832Ser	missense_variant	19/39	1	NM_172232.4	ENSP00000376443.2		Q8WWZ7-1

Frequencies

GnomAD3 genomes

AF:

0.793

AC:

120528

AN:

151936

Hom.:

48698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.628

Gnomad AMI

AF:

0.954

Gnomad AMR

AF:

0.797

Gnomad ASJ

AF:

0.855

Gnomad EAS

AF:

0.945

Gnomad SAS

AF:

0.909

Gnomad FIN

AF:

0.857

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.857

Gnomad OTH

AF:

0.796

GnomAD3 exomes

AF:

0.848

AC:

207685

AN:

244946

Hom.:

88729

AF XY:

0.855

AC XY:

113208

AN XY:

132346

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.801

Gnomad ASJ exome

AF:

0.867

Gnomad EAS exome

AF:

0.946

Gnomad SAS exome

AF:

0.900

Gnomad FIN exome

AF:

0.857

Gnomad NFE exome

AF:

0.860

Gnomad OTH exome

AF:

0.851

GnomAD4 exome

AF:

0.854

AC:

1242822

AN:

1455520

Hom.:

532303

Cov.:

AF XY:

0.857

AC XY:

620151

AN XY:

723760

show subpopulations

Gnomad4 AFR exome

AF:

0.623

Gnomad4 AMR exome

AF:

0.795

Gnomad4 ASJ exome

AF:

0.867

Gnomad4 EAS exome

AF:

0.955

Gnomad4 SAS exome

AF:

0.901

Gnomad4 FIN exome

AF:

0.853

Gnomad4 NFE exome

AF:

0.856

Gnomad4 OTH exome

AF:

0.847

GnomAD4 genome

AF:

0.793

AC:

120606

AN:

152054

Hom.:

48729

Cov.:

AF XY:

0.797

AC XY:

59215

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.629

Gnomad4 AMR

AF:

0.796

Gnomad4 ASJ

AF:

0.855

Gnomad4 EAS

AF:

0.945

Gnomad4 SAS

AF:

0.910

Gnomad4 FIN

AF:

0.857

Gnomad4 NFE

AF:

0.857

Gnomad4 OTH

AF:

0.797

Alfa

AF:

0.849

Hom.:

120426

Bravo

AF:

0.778

TwinsUK

AF:

0.855

AC:

3169

ALSPAC

AF:

0.859

AC:

3309

ESP6500AA

AF:

0.629

AC:

2769

ESP6500EA

AF:

0.855

AC:

7348

ExAC

AF:

0.847

AC:

102827

Asia WGS

AF:

0.890

AC:

3088

AN:

3472

EpiCase

AF:

0.863

EpiControl

AF:

0.862

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.048

T;T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.069

.;T;T

MetaRNN

Benign

0.0000011

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;N;.

PrimateAI

Benign

0.35

PROVEAN

Benign

0.040

N;.;.

REVEL

Benign

0.13

Sift

Benign

1.0

T;.;.

Sift4G

Benign

0.77

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.012

MPC

0.047

ClinPred

0.0011

GERP RS

2.1

Varity_R

0.025

gMVP

0.071

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over