Genetic Variant NM_019625.4:c.1381-33G>A (chr12-122941028-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_019625.4(ABCB9):c.1381-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,539,396 control chromosomes in the GnomAD database, including 133,128 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 0.34 ( 10681 hom., cov: 32)

Exomes 𝑓: 0.41 ( 122447 hom. )

Consequence

ABCB9
NM_019625.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.64

Publications

25 publications found

Variant links:

Genes affected

ABCB9 (HGNC:50): (ATP binding cassette subfamily B member 9) 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This family member functions in the translocation of peptides from the cytosol into the lysosomal lumen. Alternative splicing of this gene results in distinct isoforms which are likely to have different substrate specificities. [provided by RefSeq, Jul 2011]

ABCB9 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=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCB9	NM_019625.4	MANE Select	c.1381-33G>A	intron	N/A	NP_062571.1	Q9NP78-1
ABCB9	NM_001437843.1		c.1381-33G>A	intron	N/A	NP_001424772.1
ABCB9	NM_001438398.1		c.1252-33G>A	intron	N/A	NP_001425327.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCB9	ENST00000280560.13	TSL:1 MANE Select	c.1381-33G>A	intron	N/A	ENSP00000280560.8	Q9NP78-1
ABCB9	ENST00000542678.5	TSL:1	c.1381-33G>A	intron	N/A	ENSP00000440288.1	Q9NP78-1
ABCB9	ENST00000442833.6	TSL:1	c.1381-33G>A	intron	N/A	ENSP00000456375.1	Q9NP78-5

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51293

AN:

151892

Hom.:

10685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.423

Gnomad EAS

AF:

0.671

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.367

GnomAD2 exomes

AF:

0.430

AC:

82952

AN:

192864

AF XY:

0.439

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.427

Gnomad EAS exome

AF:

0.679

Gnomad FIN exome

AF:

0.386

Gnomad NFE exome

AF:

0.414

Gnomad OTH exome

AF:

0.435

GnomAD4 exome

AF:

0.413

AC:

573588

AN:

1387386

Hom.:

122447

Cov.:

AF XY:

0.417

AC XY:

283798

AN XY:

680806

show subpopulations

African (AFR)

AF:

0.0892

AC:

2868

AN:

32144

American (AMR)

AF:

0.433

AC:

16735

AN:

38682

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

9833

AN:

23606

East Asian (EAS)

AF:

0.663

AC:

24769

AN:

37364

South Asian (SAS)

AF:

0.509

AC:

39762

AN:

78062

European-Finnish (FIN)

AF:

0.389

AC:

19507

AN:

50162

Middle Eastern (MID)

AF:

0.420

AC:

2306

AN:

5492

European-Non Finnish (NFE)

AF:

0.408

AC:

434485

AN:

1064844

Other (OTH)

AF:

0.409

AC:

23323

AN:

57030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

17698

35396

53094

70792

88490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13996

27992

41988

55984

69980

<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:

0.337

AC:

51292

AN:

152010

Hom.:

10681

Cov.:

AF XY:

0.344

AC XY:

25567

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.105

AC:

4348

AN:

41494

American (AMR)

AF:

0.438

AC:

6681

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

1467

AN:

3472

East Asian (EAS)

AF:

0.671

AC:

3462

AN:

5158

South Asian (SAS)

AF:

0.517

AC:

2488

AN:

4808

European-Finnish (FIN)

AF:

0.387

AC:

4088

AN:

10562

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.406

AC:

27608

AN:

67954

Other (OTH)

AF:

0.367

AC:

776

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1552

3104

4657

6209

7761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.382

Hom.:

32596

Bravo

AF:

0.324

Asia WGS

AF:

0.527

AC:

1831

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.0040

(source)

DANN

Benign

0.62

PhyloP100

-3.6

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