X-75053250-AATCTT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001271696.3(ABCB7):c.*115_*119del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 940,006 control chromosomes in the GnomAD database, including 1 homozygotes. There are 106 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., 49 hem., cov: 23)
  • Exomes 𝑓: 0.00030 (1 hom. 57 hem.)
• Consequence: ABCB7 NM_001271696.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53

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-75053250-AATCTT-A is Benign according to our data. Variant chrX-75053250-AATCTT-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00213 (240/112536) while in subpopulation AFR AF= 0.00687 (213/30993). AF 95% confidence interval is 0.00612. There are 0 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 49 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB7	NM_001271696.3	c.*115_*119del		3_prime_UTR_variant	16/16	ENST00000373394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB7	ENST00000373394.8	c.*115_*119del		3_prime_UTR_variant	16/16	1	NM_001271696.3	A1

Frequencies

GnomAD3 genomes AF: 0.00213 AC: 240 AN: 112482 Hom.: 0 Cov.: 23 AF XY: 0.00141 AC XY: 49 AN XY: 34634

Gnomad AFR AF: 0.00689

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000244

Gnomad OTH AF: 0.00132

GnomAD4 exome AF: 0.000296 AC: 245 AN: 827470 Hom.: 1 AF XY: 0.000254 AC XY: 57 AN XY: 224294

Gnomad4 AFR exome AF: 0.00722

Gnomad4 AMR exome AF: 0.000679

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: 0.0000883

Gnomad4 OTH exome AF: 0.000764

GnomAD4 genome AF: 0.00213 AC: 240 AN: 112536 Hom.: 0 Cov.: 23 AF XY: 0.00141 AC XY: 49 AN XY: 34698

Gnomad4 AFR AF: 0.00687

Gnomad4 AMR AF: 0.00113

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000244

Gnomad4 OTH AF: 0.00131

Alfa AF: 0.00206 Hom.: 8

Bravo AF: 0.00230

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ABCB7: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs765754237; hg19: chrX-74273085;