rs2303922

Variant names:

• chr7-151028635-A-C
• rs2303922
• NM_007188.5:c.95+25A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-151028635-A-C
• chr7-151028635-A-G
• chr7-151028635-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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]

ENSG00000243433 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABCB8	NM_007188.5	c.95+25A>C		intron_variant	Intron 1 of 15	ENST00000358849.9	NP_009119.2
ABCB8	NM_001282291.2	c.95+25A>C		intron_variant	Intron 1 of 16		NP_001269220.1
ABCB8	NM_001282292.2	c.95+25A>C		intron_variant	Intron 1 of 15		NP_001269221.1
ABCB8	NM_001282293.2	c.144+25A>C		intron_variant	Intron 1 of 14		NP_001269222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB8	ENST00000358849.9	c.95+25A>C		intron_variant	Intron 1 of 15	1	NM_007188.5	ENSP00000351717.4

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

GnomAD2 exomes AF: 0.342 AC: 79296 AN: 231842 AF XY: 0.345

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 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

African (AFR) AF: 0.525 AC: 17523 AN: 33354

American (AMR) AF: 0.213 AC: 9277 AN: 43482

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9356 AN: 26030

East Asian (EAS) AF: 0.310 AC: 12228 AN: 39408

South Asian (SAS) AF: 0.391 AC: 33299 AN: 85148

European-Finnish (FIN) AF: 0.336 AC: 17177 AN: 51162

Middle Eastern (MID) AF: 0.325 AC: 1516 AN: 4660

European-Non Finnish (NFE) AF: 0.367 AC: 406723 AN: 1108936

Other (OTH) AF: 0.368 AC: 22036 AN: 59950

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

African (AFR) AF: 0.518 AC: 21493 AN: 41484

American (AMR) AF: 0.284 AC: 4351 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1220 AN: 3470

East Asian (EAS) AF: 0.288 AC: 1480 AN: 5134

South Asian (SAS) AF: 0.388 AC: 1866 AN: 4814

European-Finnish (FIN) AF: 0.333 AC: 3531 AN: 10594

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24617 AN: 67962

Other (OTH) AF: 0.380 AC: 804 AN: 2114

Alfa AF: 0.358 Hom.: 19124

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
PhyloP100		-0.64
PromoterAI		-0.041	Neutral
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: rs2303922; hg19: chr7-150725722; COSMIC: COSV52508665; COSMIC: COSV52508665;