rs6647617

Variant names:

• chrX-75056294-G-A
• rs6647617
• NM_001271696.3:c.2044-2709C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• X-linked sideroblastic anemia with ataxia

  Inheritance: XL, XLR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Illumina, Labcorp Genetics (formerly Invitae), G2P
• mitochondrial disease

  Inheritance: XL Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271696.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB7	NM_001271696.3	MANE Select	c.2044-2709C>T		intron	N/A	NP_001258625.1	O75027-1
	ABCB7	NM_004299.6		c.2047-2709C>T		intron	N/A	NP_004290.2
	ABCB7	NM_001271698.3		c.1966-2709C>T		intron	N/A	NP_001258627.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB7	ENST00000373394.8	TSL:1 MANE Select	c.2044-2709C>T		intron	N/A	ENSP00000362492.3	O75027-1
	ABCB7	ENST00000253577.9	TSL:1	c.2047-2709C>T		intron	N/A	ENSP00000253577.3	O75027-2
	ABCB7	ENST00000620875.5	TSL:1	c.1927-2709C>T		intron	N/A	ENSP00000479985.1	A0A087WW65

Frequencies

GnomAD3 genomes AF: 0.283 AC: 31389 AN: 110910 Hom.: 6308 Cov.: 22

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

African (AFR) AF: 0.649 AC: 19711 AN: 30393

American (AMR) AF: 0.311 AC: 3258 AN: 10484

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 213 AN: 2634

East Asian (EAS) AF: 0.905 AC: 3139 AN: 3470

South Asian (SAS) AF: 0.324 AC: 847 AN: 2613

European-Finnish (FIN) AF: 0.0654 AC: 390 AN: 5964

Middle Eastern (MID) AF: 0.107 AC: 23 AN: 215

European-Non Finnish (NFE) AF: 0.0653 AC: 3458 AN: 52994

Other (OTH) AF: 0.252 AC: 382 AN: 1514

Alfa AF: 0.152 Hom.: 1242

Bravo AF: 0.327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.56
DANN	Benign	0.64
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6647617; hg19: chrX-74276129;