dbSNP rs7296418: ABCB9:c.-88+5826G>A (chr12-122973072-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 ENST00000542678.5(ABCB9):c.-88+5826G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,132 control chromosomes in the GnomAD database, including 36,508 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 0.69 ( 36499 hom., cov: 32)

Exomes 𝑓: 0.73 ( 9 hom. )

Consequence

ABCB9
ENST00000542678.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.525

Publications

49 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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
ABCB9	XM_017019103.2 link	c.-117G>A	5_prime_UTR_variant	Exon 2 of 13	XP_016874592.1
ABCB9	NM_001437843.1 link	c.-88+1643G>A	intron_variant	Intron 1 of 11	NP_001424772.1
ABCB9	NM_001438398.1 link	c.-88+1443G>A	intron_variant	Intron 1 of 10	NP_001425327.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
ABCB9	ENST00000542678.5 link	c.-88+5826G>A	intron_variant	Intron 1 of 11	1	ENSP00000440288.1
ABCB9	ENST00000622723.1 link	n.162G>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
ABCB9	ENST00000543935.1 link	c.-117G>A	5_prime_UTR_variant	Exon 2 of 3	4	ENSP00000443382.1
ABCB9	ENST00000392439.7 link	c.-88+1643G>A	intron_variant	Intron 1 of 11	5	ENSP00000376234.3

Frequencies

GnomAD3 genomes

AF:

0.691

AC:

105071

AN:

151984

Hom.:

36478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.697

Gnomad ASJ

AF:

0.637

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.689

GnomAD4 exome

AF:

0.733

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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)

AF:

0.875

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.688

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000388202), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.313

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.691

AC:

105136

AN:

152102

Hom.:

36499

Cov.:

AF XY:

0.690

AC XY:

51308

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.668

AC:

27719

AN:

41484

American (AMR)

AF:

0.696

AC:

10626

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.637

AC:

2209

AN:

3470

East Asian (EAS)

AF:

0.674

AC:

3484

AN:

5170

South Asian (SAS)

AF:

0.587

AC:

2830

AN:

4820

European-Finnish (FIN)

AF:

0.718

AC:

7600

AN:

10584

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.711

AC:

48358

AN:

67986

Other (OTH)

AF:

0.687

AC:

1450

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1697

3394

5090

6787

8484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<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:

0.698

Hom.:

68980

Bravo

AF:

0.686

Asia WGS

AF:

0.608

AC:

2117

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.51

(source)

DANN

Benign

0.70

PhyloP100

-0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over