rs2303922

chr7-151028635-A-Cchr7-151028635-A-G

Variant summary

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

The NM_007188.5(ABCB8):c.95+25A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,604,200 control chromosomes in the GnomAD database, including 110,374 homozygotes. 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 0.39 (12196 hom., cov: 33)
  • Exomes 𝑓: 0.36 (98178 hom.)
• Consequence: ABCB8 NM_007188.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

Genes affected

ABCB8 (HGNC:49): (ATP binding cassette subfamily B member 8) This nuclear gene encodes a multi-pass membrane protein that is targeted to the mitochondrial inner membrane. The encoded protein is an ATP-dependent transporter that may mediate the passage of organic and inorganic molecules out of the mitochondria. Loss of function of the related gene in mouse results in a disruption of iron homeostasis between the mitochondria and cytosol. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB8	NM_007188.5	c.95+25A>C		intron_variant		ENST00000358849.9
ABCB8	NM_001282291.2	c.95+25A>C		intron_variant
ABCB8	NM_001282292.2	c.95+25A>C		intron_variant
ABCB8	NM_001282293.2	c.144+25A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB8	ENST00000358849.9	c.95+25A>C		intron_variant		1	NM_007188.5	P1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59720 AN: 151952 Hom.: 12176 Cov.: 33

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.379

GnomAD3 exomes AF: 0.342 AC: 79296 AN: 231842 Hom.: 13936 AF XY: 0.345 AC XY: 43520 AN XY: 126228

Gnomad AFR exome AF: 0.525

Gnomad AMR exome AF: 0.209

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.290

Gnomad SAS exome AF: 0.388

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.354

Gnomad OTH exome AF: 0.339

GnomAD4 exome AF: 0.364 AC: 529135 AN: 1452130 Hom.: 98178 Cov.: 40 AF XY: 0.365 AC XY: 263287 AN XY: 721814

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.393 AC: 59788 AN: 152070 Hom.: 12196 Cov.: 33 AF XY: 0.386 AC XY: 28716 AN XY: 74350

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.380

Alfa AF: 0.351 Hom.: 13480

Bravo AF: 0.393

Asia WGS AF: 0.363 AC: 1262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.3
Dann	Benign	0.65

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: rs2303922; hg19: chr7-150725722; COSMIC: COSV52508665; COSMIC: COSV52508665;