rs536009

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

37 publications found

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 Gene-Disease associations (from GenCC):

gingival fibromatosis-hypertrichosis syndrome
Inheritance: AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Ambry Genetics
ventricular tachycardia, familial
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ABCA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172232.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA5	NM_172232.4	MANE Select	c.2494G>T	p.Ala832Ser	missense	Exon 19 of 39	NP_758424.1
	ABCA5	NM_018672.5		c.2494G>T	p.Ala832Ser	missense	Exon 18 of 38	NP_061142.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCA5	ENST00000392676.8	TSL:1 MANE Select	c.2494G>T	p.Ala832Ser	missense	Exon 19 of 39	ENSP00000376443.2
ABCA5	ENST00000588877.5	TSL:1	c.2494G>T	p.Ala832Ser	missense	Exon 18 of 38	ENSP00000467882.1
ABCA5	ENST00000586995.5	TSL:1	n.*244G>T		non_coding_transcript_exon	Exon 13 of 32	ENSP00000467251.1

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

GnomAD2 exomes

AF:

0.848

AC:

207685

AN:

244946

AF XY:

0.855

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 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

African (AFR)

AF:

0.623

AC:

20666

AN:

33164

American (AMR)

AF:

0.795

AC:

34300

AN:

43128

Ashkenazi Jewish (ASJ)

AF:

0.867

AC:

22474

AN:

25934

East Asian (EAS)

AF:

0.955

AC:

37736

AN:

39504

South Asian (SAS)

AF:

0.901

AC:

76066

AN:

84444

European-Finnish (FIN)

AF:

0.853

AC:

45463

AN:

53282

Middle Eastern (MID)

AF:

0.850

AC:

4876

AN:

5738

European-Non Finnish (NFE)

AF:

0.856

AC:

950296

AN:

1110158

Other (OTH)

AF:

0.847

AC:

50945

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

9725

19450

29174

38899

48624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21152

42304

63456

84608

105760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.793

AC:

120606

AN:

152054

Hom.:

48729

Cov.:

AF XY:

0.797

AC XY:

59215

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.629

AC:

26070

AN:

41460

American (AMR)

AF:

0.796

AC:

12167

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.855

AC:

2967

AN:

3470

East Asian (EAS)

AF:

0.945

AC:

4893

AN:

5180

South Asian (SAS)

AF:

0.910

AC:

4385

AN:

4820

European-Finnish (FIN)

AF:

0.857

AC:

9051

AN:

10562

Middle Eastern (MID)

AF:

0.867

AC:

255

AN:

294

European-Non Finnish (NFE)

AF:

0.857

AC:

58267

AN:

67972

Other (OTH)

AF:

0.797

AC:

1681

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1215

2429

3644

4858

6073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.842

Hom.:

228997

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.048

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.069

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

0.32

PrimateAI

Benign

0.35

PROVEAN

Benign

0.040

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

0.77

Polyphen

0.0

Vest4

0.012

MPC

0.047

ClinPred

0.0011

GERP RS

2.1

Varity_R

0.025

gMVP

0.071

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over