X-75053609-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001271696.3(ABCB7):c.2044-24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,167,924 control chromosomes in the GnomAD database, including 37 homozygotes. There are 769 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (21 hom., 391 hem., cov: 23)
  • Exomes 𝑓: 0.0014 (16 hom. 378 hem.)
• Consequence: ABCB7 NM_001271696.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.137

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant X-75053609-C-T is Benign according to our data. Variant chrX-75053609-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1218538.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1392/112395) while in subpopulation AFR AF= 0.0418 (1294/30924). AF 95% confidence interval is 0.0399. There are 21 homozygotes in gnomad4. There are 391 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB7	NM_001271696.3	c.2044-24G>A		intron_variant		ENST00000373394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB7	ENST00000373394.8	c.2044-24G>A		intron_variant		1	NM_001271696.3	A1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1386 AN: 112346 Hom.: 21 Cov.: 23 AF XY: 0.0111 AC XY: 384 AN XY: 34516

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00574

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.000356

Gnomad OTH AF: 0.0112

GnomAD3 exomes AF: 0.00357 AC: 427 AN: 119461 Hom.: 3 AF XY: 0.00229 AC XY: 92 AN XY: 40195

Gnomad AFR exome AF: 0.0438

Gnomad AMR exome AF: 0.00248

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000695

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000321

Gnomad OTH exome AF: 0.00205

GnomAD4 exome AF: 0.00135 AC: 1430 AN: 1055529 Hom.: 16 Cov.: 29 AF XY: 0.00110 AC XY: 378 AN XY: 343305

Gnomad4 AFR exome AF: 0.0405

Gnomad4 AMR exome AF: 0.00269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000263

Gnomad4 NFE exome AF: 0.000182

Gnomad4 OTH exome AF: 0.00405

GnomAD4 genome AF: 0.0124 AC: 1392 AN: 112395 Hom.: 21 Cov.: 23 AF XY: 0.0113 AC XY: 391 AN XY: 34575

Gnomad4 AFR AF: 0.0418

Gnomad4 AMR AF: 0.00573

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000356

Gnomad4 OTH AF: 0.0111

Alfa AF: 0.00587 Hom.: 23

Bravo AF: 0.0142

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

GeneDx

Jul 07, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	9.5
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: rs142425608; hg19: chrX-74273444;