Variant 7-151033625-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007188.5(ABCB8):c.116G>A(p.Ser39Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,587,502 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 168 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 143 hom. )

Consequence

ABCB8
NM_007188.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.36

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024946928).

BP6

Variant 7-151033625-G-A is Benign according to our data. Variant chr7-151033625-G-A is described in ClinVar as [Benign]. Clinvar id is 769736.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABCB8	NM_007188.5 linkuse as main transcript	c.116G>A	p.Ser39Asn	missense_variant	2/16	ENST00000358849.9
ABCB8	NM_001282291.2 linkuse as main transcript	c.167G>A	p.Ser56Asn	missense_variant	3/17
ABCB8	NM_001282292.2 linkuse as main transcript	c.116G>A	p.Ser39Asn	missense_variant	2/16
ABCB8	NM_001282293.2 linkuse as main transcript	c.145-648G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB8	ENST00000358849.9 linkuse as main transcript	c.116G>A	p.Ser39Asn	missense_variant	2/16	1	NM_007188.5	P1	Q9NUT2-2

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3804

AN:

152132

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0849

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.00748

AC:

1743

AN:

232934

Hom.:

AF XY:

0.00570

AC XY:

718

AN XY:

126000

show subpopulations

Gnomad AFR exome

AF:

0.0861

Gnomad AMR exome

AF:

0.00620

Gnomad ASJ exome

AF:

0.00403

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000250

Gnomad FIN exome

AF:

0.0000484

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.00427

GnomAD4 exome

AF:

0.00314

AC:

4508

AN:

1435252

Hom.:

143

Cov.:

AF XY:

0.00282

AC XY:

2001

AN XY:

710686

show subpopulations

Gnomad4 AFR exome

AF:

0.0870

Gnomad4 AMR exome

AF:

0.00659

Gnomad4 ASJ exome

AF:

0.00337

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.000287

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.000665

Gnomad4 OTH exome

AF:

0.00784

GnomAD4 genome

AF:

0.0251

AC:

3818

AN:

152250

Hom.:

168

Cov.:

AF XY:

0.0243

AC XY:

1808

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0850

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.00582

Hom.:

Bravo

AF:

0.0293

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0772

AC:

340

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00874

AC:

1061

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.61

T;T;T;T;T;T

MetaRNN

Benign

0.0025

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.5

N;N;N;N;N;N

REVEL

Benign

0.085

Sift

Uncertain

0.0030

D;D;D;D;D;D

Sift4G

Uncertain

0.023

D;T;T;T;D;D

Polyphen

0.28, 0.36

.;B;B;.;.;B

Vest4

0.14, 0.16, 0.23, 0.13, 0.17

MVP

0.89

MPC

0.21

ClinPred

0.029

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.044

gMVP

0.28

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

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