Variant chrX-75053854-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001271696.3(ABCB7):c.2044-269C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 111,515 control chromosomes in the GnomAD database, including 17 homozygotes. There are 346 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.013 ( 17 hom., 346 hem., cov: 23)

Consequence

ABCB7
NM_001271696.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.466

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-75053854-G-C is Benign according to our data. Variant chrX-75053854-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1208344.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1463/111515) while in subpopulation AFR AF= 0.0452 (1389/30721). AF 95% confidence interval is 0.0432. There are 17 homozygotes in gnomad4. There are 346 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB7	NM_001271696.3 link	c.2044-269C>G		intron_variant		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.2044-269C>G		intron_variant		1	NM_001271696.3	ENSP00000362492.3		O75027-1

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1458

AN:

111462

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

344

AN XY:

33684

show subpopulations

Gnomad AFR

AF:

0.0451

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00428

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000376

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000188

Gnomad OTH

AF:

0.0119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0131

AC:

1463

AN:

111515

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

346

AN XY:

33747

show subpopulations

Gnomad4 AFR

AF:

0.0452

Gnomad4 AMR

AF:

0.00427

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000377

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000189

Gnomad4 OTH

AF:

0.0117

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.0155

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.34

DANN

Benign

0.66

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