Genetic Variant ABCB8:c.1765+135G>C (chr7-151042243-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_007188.5(ABCB8):c.1765+135G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,335,568 control chromosomes in the GnomAD database, including 276,679 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 ( 36703 hom., cov: 32)

Exomes 𝑓: 0.63 ( 239976 hom. )

Consequence

ABCB8
NM_007188.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17

Publications

9 publications found

Variant links:

Genes affected

ABCB8 (HGNC:49): (ATP binding cassette subfamily B member 8) This nuclear gene encodes a multi-pass membrane protein that is targeted to the mitochondrial inner membrane. The encoded protein is an ATP-dependent transporter that may mediate the passage of organic and inorganic molecules out of the mitochondria. Loss of function of the related gene in mouse results in a disruption of iron homeostasis between the mitochondria and cytosol. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ABCB8 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007188.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ABCB8	NM_007188.5	MANE Select	c.1765+135G>C	intron	N/A	NP_009119.2
ABCB8	NM_001282291.2		c.1816+135G>C	intron	N/A	NP_001269220.1
ABCB8	NM_001282292.2		c.1765+135G>C	intron	N/A	NP_001269221.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ABCB8	ENST00000358849.9	TSL:1 MANE Select	c.1765+135G>C	intron	N/A	ENSP00000351717.4
ABCB8	ENST00000498578.5	TSL:1	c.1765+135G>C	intron	N/A	ENSP00000418271.1
ABCB8	ENST00000297504.10	TSL:2	c.1816+135G>C	intron	N/A	ENSP00000297504.6

Frequencies

GnomAD3 genomes

AF:

0.688

AC:

104498

AN:

151958

Hom.:

36652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.830

Gnomad AMI

AF:

0.563

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.611

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.615

Gnomad OTH

AF:

0.679

GnomAD4 exome

AF:

0.635

AC:

751052

AN:

1183492

Hom.:

239976

AF XY:

0.633

AC XY:

370649

AN XY:

585434

show subpopulations

African (AFR)

AF:

0.842

AC:

23306

AN:

27674

American (AMR)

AF:

0.779

AC:

24365

AN:

31292

Ashkenazi Jewish (ASJ)

AF:

0.631

AC:

12573

AN:

19930

East Asian (EAS)

AF:

0.716

AC:

26364

AN:

36800

South Asian (SAS)

AF:

0.636

AC:

43440

AN:

68294

European-Finnish (FIN)

AF:

0.612

AC:

21291

AN:

34812

Middle Eastern (MID)

AF:

0.604

AC:

2072

AN:

3428

European-Non Finnish (NFE)

AF:

0.620

AC:

565070

AN:

910734

Other (OTH)

AF:

0.645

AC:

32571

AN:

50528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

12859

25719

38578

51438

64297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15016

30032

45048

60064

75080

<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:

0.688

AC:

104605

AN:

152076

Hom.:

36703

Cov.:

AF XY:

0.686

AC XY:

50982

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.830

AC:

34449

AN:

41482

American (AMR)

AF:

0.712

AC:

10883

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

2214

AN:

3468

East Asian (EAS)

AF:

0.709

AC:

3669

AN:

5174

South Asian (SAS)

AF:

0.627

AC:

3026

AN:

4826

European-Finnish (FIN)

AF:

0.611

AC:

6456

AN:

10574

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.615

AC:

41777

AN:

67956

Other (OTH)

AF:

0.677

AC:

1428

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1622

3244

4866

6488

8110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.536

Hom.:

1420

Bravo

AF:

0.707

Asia WGS

AF:

0.678

AC:

2359

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.90

(source)

DANN

Benign

0.69

PhyloP100

-1.2

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