X-75060016-TATA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001271696.3(ABCB7):c.2043+204_2043+206del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 112,029 control chromosomes in the GnomAD database, including 115 homozygotes. There are 750 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.028 (115 hom., 750 hem., cov: 21)
• Consequence: ABCB7 NM_001271696.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.09

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-75060016-TATA-T is Benign according to our data. Variant chrX-75060016-TATA-T is described in ClinVar as [Benign]. Clinvar id is 1292863.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB7	NM_001271696.3	c.2043+204_2043+206del		intron_variant		ENST00000373394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB7	ENST00000373394.8	c.2043+204_2043+206del		intron_variant		1	NM_001271696.3	A1

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 3168 AN: 111979 Hom.: 115 Cov.: 21 AF XY: 0.0219 AC XY: 749 AN XY: 34167

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00809

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000366

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000263

Gnomad OTH AF: 0.0206

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

GnomAD4 genome AF: 0.0283 AC: 3171 AN: 112029 Hom.: 115 Cov.: 21 AF XY: 0.0219 AC XY: 750 AN XY: 34227

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.00808

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000367

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000263

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0216 Hom.: 62

Bravo AF: 0.0327

Asia WGS AF: 0.00199 AC: 5 AN: 2516

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs200468258; hg19: chrX-74279851;