X-75060206-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001271696.3(ABCB7):c.2043+17T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,157,106 control chromosomes in the GnomAD database, including 1,813 homozygotes. There are 4,876 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (925 hom., 2439 hem., cov: 22)
  • Exomes 𝑓: 0.0090 (888 hom. 2437 hem.)
• Consequence: ABCB7 NM_001271696.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.828

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-75060206-A-T is Benign according to our data. Variant chrX-75060206-A-T is described in ClinVar as [Benign]. Clinvar id is 136247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB7	NM_001271696.3	c.2043+17T>A		intron_variant		ENST00000373394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB7	ENST00000373394.8	c.2043+17T>A		intron_variant		1	NM_001271696.3	A1

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 9067 AN: 111532 Hom.: 922 Cov.: 22 AF XY: 0.0721 AC XY: 2432 AN XY: 33724

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0325

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000736

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0297

Gnomad NFE AF: 0.000734

Gnomad OTH AF: 0.0620

GnomAD3 exomes AF: 0.0239 AC: 4307 AN: 179854 Hom.: 442 AF XY: 0.0154 AC XY: 998 AN XY: 64754

Gnomad AFR exome AF: 0.298

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000271

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000526

Gnomad OTH exome AF: 0.00966

GnomAD4 exome AF: 0.00897 AC: 9378 AN: 1045523 Hom.: 888 Cov.: 22 AF XY: 0.00756 AC XY: 2437 AN XY: 322309

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.0149

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000335

Gnomad4 SAS exome AF: 0.000854

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000360

Gnomad4 OTH exome AF: 0.0204

GnomAD4 genome AF: 0.0813 AC: 9075 AN: 111583 Hom.: 925 Cov.: 22 AF XY: 0.0722 AC XY: 2439 AN XY: 33785

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.0324

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000738

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000734

Gnomad4 OTH AF: 0.0613

Alfa AF: 0.0421 Hom.: 257

Bravo AF: 0.0945

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 24, 2012

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	13
Dann	Benign	0.78

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: rs73502896; hg19: chrX-74280041;