chr7-151033735-G-A

Variant names:

• chr7-151033735-G-A
• rs1796227143
• NM_007188.5:c.226G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007188.5(ABCB8):​c.226G>A​(p.Gly76Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB8 NM_007188.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB8	NM_007188.5	c.226G>A	p.Gly76Arg	missense_variant	Exon 2 of 16	ENST00000358849.9	NP_009119.2
ABCB8	NM_001282291.2	c.277G>A	p.Gly93Arg	missense_variant	Exon 3 of 17		NP_001269220.1
ABCB8	NM_001282292.2	c.226G>A	p.Gly76Arg	missense_variant	Exon 2 of 16		NP_001269221.1
ABCB8	NM_001282293.2	c.145-538G>A		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.226G>A	p.Gly76Arg	missense_variant	Exon 2 of 16	1	NM_007188.5	ENSP00000351717.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.226G>A (p.G76R) alteration is located in exon 2 (coding exon 2) of the ABCB8 gene. This alteration results from a G to A substitution at nucleotide position 226, causing the glycine (G) at amino acid position 76 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	.;.;T;.;.;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D
M_CAP	Pathogenic	0.37	D
MetaRNN	Uncertain	0.61	D;D;D;D;D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	1.9	.;.;L;.;.;.
PhyloP100		2.8
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-7.9	D;N;N;N;N;N
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D
Polyphen		0.97, 0.99	.;D;D;.;.;D
Vest4		0.54, 0.51, 0.56, 0.41, 0.47
MutPred		0.57		.;.;Gain of MoRF binding (P = 0.0031);.;.;.;
MVP		0.91
MPC		0.70
ClinPred		1.0	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.47
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1796227143; hg19: chr7-150730822;