Genetic Variant ABCA8:c.4039-1474G>C (chr17-68879153-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001288985.2(ABCA8):c.4039-1474G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,138 control chromosomes in the GnomAD database, including 12,678 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 12678 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

ABCA8
NM_001288985.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.847

Publications

61 publications found

Variant links:

Genes affected

ABCA8 (HGNC:38): (ATP binding cassette subfamily A member 8) 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. The encoded protein may regulate lipid metabolism and be involved in the formation and maintenance of myelin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ABCA8 links:

LOC105371874 (HGNC:):

LOC105371874 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA8	NM_001288985.2 link	c.4039-1474G>C		intron_variant	Intron 32 of 39	ENST00000586539.6	NP_001275914.1	O94911-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA8	ENST00000586539.6 link	c.4039-1474G>C		intron_variant	Intron 32 of 39	1	NM_001288985.2	ENSP00000467271.1		O94911-3

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59804

AN:

152020

Hom.:

12663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.553

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.447

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.388

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.393

AC:

59864

AN:

152138

Hom.:

12678

Cov.:

AF XY:

0.393

AC XY:

29238

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.553

AC:

22961

AN:

41498

American (AMR)

AF:

0.355

AC:

5423

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1404

AN:

3468

East Asian (EAS)

AF:

0.447

AC:

2313

AN:

5174

South Asian (SAS)

AF:

0.316

AC:

1525

AN:

4828

European-Finnish (FIN)

AF:

0.328

AC:

3475

AN:

10586

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.317

AC:

21550

AN:

67978

Other (OTH)

AF:

0.388

AC:

820

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1796

3592

5388

7184

8980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.214

Hom.:

491

Bravo

AF:

0.403

Asia WGS

AF:

0.374

AC:

1299

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.48

(source)

DANN

Benign

0.36

PhyloP100

-0.85

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over