Variant X-75053450-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001271696.3(ABCB7):c.2179A>T(p.Ile727Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,492 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

ABCB7
NM_001271696.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.356

Variant links:

Genes affected

ABCB7 (HGNC:48): (ATP binding cassette subfamily B member 7) 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 gene encodes a half-transporter involved in the transport of heme from the mitochondria to the cytosol. With iron/sulfur cluster precursors as its substrates, this protein may play a role in metal homeostasis. Mutations in this gene have been associated with mitochondrial iron accumulation and isodicentric (X)(q13) and sideroblastic anemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]

ABCB7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019729167).

BP6

Variant X-75053450-T-A is Benign according to our data. Variant chrX-75053450-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3607848.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB7	NM_001271696.3 link	c.2179A>T	p.Ile727Leu	missense_variant	16/16	ENST00000373394.8	NP_001258625.1	O75027-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB7	ENST00000373394.8 link	c.2179A>T	p.Ile727Leu	missense_variant	16/16	1	NM_001271696.3	ENSP00000362492.3		O75027-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

183276

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1097492

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362868

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.12

DANN

Benign

0.74

DEOGEN2

Benign

0.24

.;.;.;T;T;.

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.45

.;T;T;T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.020

T;T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

-0.20

.;.;.;N;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.23

.;N;N;N;.;N

REVEL

Benign

0.20

Sift

Benign

0.84

.;T;T;T;.;T

Sift4G

Benign

1.0

.;T;T;T;T;T

Polyphen

0.0

B;B;.;B;.;.

Vest4

0.16, 0.17, 0.16, 0.17

MutPred

0.17

.;.;.;Gain of ubiquitination at K724 (P = 0.1008);.;.;

MVP

0.28

MPC

1.1

ClinPred

0.026

GERP RS

-12

Varity_R

0.086

gMVP

0.64

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over