Variant 7-151033879-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007188.5(ABCB8):c.370C>G(p.Leu124Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00902 in 1,610,238 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0092 ( 82 hom. )

Consequence

ABCB8
NM_007188.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.01

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009119093).

BP6

Variant 7-151033879-C-G is Benign according to our data. Variant chr7-151033879-C-G is described in ClinVar as [Benign]. Clinvar id is 774196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABCB8	NM_007188.5 linkuse as main transcript	c.370C>G	p.Leu124Val	missense_variant	2/16	ENST00000358849.9
ABCB8	NM_001282291.2 linkuse as main transcript	c.421C>G	p.Leu141Val	missense_variant	3/17
ABCB8	NM_001282292.2 linkuse as main transcript	c.370C>G	p.Leu124Val	missense_variant	2/16
ABCB8	NM_001282293.2 linkuse as main transcript	c.145-394C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB8	ENST00000358849.9 linkuse as main transcript	c.370C>G	p.Leu124Val	missense_variant	2/16	1	NM_007188.5	P1	Q9NUT2-2

Frequencies

GnomAD3 genomes

AF:

0.00689

AC:

1048

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00988

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00664

AC:

1636

AN:

246348

Hom.:

AF XY:

0.00669

AC XY:

892

AN XY:

133268

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00219

Gnomad ASJ exome

AF:

0.00336

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00268

Gnomad FIN exome

AF:

0.00969

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00332

GnomAD4 exome

AF:

0.00924

AC:

13472

AN:

1457960

Hom.:

Cov.:

AF XY:

0.00900

AC XY:

6524

AN XY:

724858

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.00214

Gnomad4 ASJ exome

AF:

0.00366

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00255

Gnomad4 FIN exome

AF:

0.00824

Gnomad4 NFE exome

AF:

0.0110

Gnomad4 OTH exome

AF:

0.00646

GnomAD4 genome

AF:

0.00688

AC:

1047

AN:

152278

Hom.:

Cov.:

AF XY:

0.00626

AC XY:

466

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00988

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00708

Hom.:

Bravo

AF:

0.00605

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0103

AC:

ExAC

AF:

0.00661

AC:

802

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00982

EpiControl

AF:

0.00915

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	ABCB8: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;T;.;.;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.85

D;D;D;D;D

MetaRNN

Benign

0.0091

T;T;T;T;T

MetaSVM

Uncertain

0.21

MutationAssessor

Benign

1.9

.;L;.;.;.

MutationTaster

Benign

0.99

D;D;D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.3

N;N;N;N;N

REVEL

Uncertain

0.39

Sift

Benign

0.10

T;T;T;T;T

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.72

P;P;.;.;D

Vest4

0.51

MVP

0.97

MPC

0.58

ClinPred

0.018

GERP RS

4.1

Varity_R

0.36

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over