rs6647617

Positions:

• chrX-75056294-G-A
• chrX-75056294-G-C
• chrX-75056294-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001271696.3(ABCB7):​c.2044-2709C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 110,963 control chromosomes in the GnomAD database, including 6,316 homozygotes. There are 9,193 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6316 hom., 9193 hem., cov: 22)
• Consequence: ABCB7 NM_001271696.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB7	NM_001271696.3	c.2044-2709C>T		intron_variant		ENST00000373394.8	NP_001258625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB7	ENST00000373394.8	c.2044-2709C>T		intron_variant		1	NM_001271696.3	ENSP00000362492	A1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 31389 AN: 110910 Hom.: 6308 Cov.: 22 AF XY: 0.276 AC XY: 9161 AN XY: 33164

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.283 AC: 31433 AN: 110963 Hom.: 6316 Cov.: 22 AF XY: 0.277 AC XY: 9193 AN XY: 33227

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.0809

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.0654

Gnomad4 NFE AF: 0.0653

Gnomad4 OTH AF: 0.252

Alfa AF: 0.152 Hom.: 1242

Bravo AF: 0.327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.56
DANN	Benign	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

Other links and lift over

dbSNP: rs6647617; hg19: chrX-74276129;