7-151042243-G-C

Variant names:

• chr7-151042243-G-C
• rs2303928
• NM_007188.5:c.1765+135G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007188.5(ABCB8):​c.1765+135G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,335,568 control chromosomes in the GnomAD database, including 276,679 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 0.69 (36703 hom., cov: 32)
  • Exomes 𝑓: 0.63 (239976 hom.)
• Consequence: ABCB8 NM_007188.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB8	NM_007188.5	c.1765+135G>C		intron_variant	Intron 14 of 15	ENST00000358849.9	NP_009119.2
ABCB8	NM_001282291.2	c.1816+135G>C		intron_variant	Intron 15 of 16		NP_001269220.1
ABCB8	NM_001282292.2	c.1765+135G>C		intron_variant	Intron 14 of 15		NP_001269221.1
ABCB8	NM_001282293.2	c.1501+135G>C		intron_variant	Intron 13 of 14		NP_001269222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB8	ENST00000358849.9	c.1765+135G>C		intron_variant	Intron 14 of 15	1	NM_007188.5	ENSP00000351717.4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104498 AN: 151958 Hom.: 36652 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.679

GnomAD4 exome AF: 0.635 AC: 751052 AN: 1183492 Hom.: 239976 AF XY: 0.633 AC XY: 370649 AN XY: 585434

African (AFR) AF: 0.842 AC: 23306 AN: 27674

American (AMR) AF: 0.779 AC: 24365 AN: 31292

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 12573 AN: 19930

East Asian (EAS) AF: 0.716 AC: 26364 AN: 36800

South Asian (SAS) AF: 0.636 AC: 43440 AN: 68294

European-Finnish (FIN) AF: 0.612 AC: 21291 AN: 34812

Middle Eastern (MID) AF: 0.604 AC: 2072 AN: 3428

European-Non Finnish (NFE) AF: 0.620 AC: 565070 AN: 910734

Other (OTH) AF: 0.645 AC: 32571 AN: 50528

GnomAD4 genome AF: 0.688 AC: 104605 AN: 152076 Hom.: 36703 Cov.: 32 AF XY: 0.686 AC XY: 50982 AN XY: 74350

African (AFR) AF: 0.830 AC: 34449 AN: 41482

American (AMR) AF: 0.712 AC: 10883 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2214 AN: 3468

East Asian (EAS) AF: 0.709 AC: 3669 AN: 5174

South Asian (SAS) AF: 0.627 AC: 3026 AN: 4826

European-Finnish (FIN) AF: 0.611 AC: 6456 AN: 10574

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41777 AN: 67956

Other (OTH) AF: 0.677 AC: 1428 AN: 2108

Alfa AF: 0.536 Hom.: 1420

Bravo AF: 0.707

Asia WGS AF: 0.678 AC: 2359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.69
PhyloP100		-1.2
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: rs2303928; hg19: chr7-150739330; COSMIC: COSV52504702; COSMIC: COSV52504702;