chr7-151033645-G-T

Variant names:

• chr7-151033645-G-T
• rs566864336
• NM_007188.5:c.136G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007188.5(ABCB8):​c.136G>T​(p.Val46Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ABCB8 NM_007188.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042604536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB8	NM_007188.5	c.136G>T	p.Val46Leu	missense_variant	Exon 2 of 16	ENST00000358849.9	NP_009119.2
ABCB8	NM_001282291.2	c.187G>T	p.Val63Leu	missense_variant	Exon 3 of 17		NP_001269220.1
ABCB8	NM_001282292.2	c.136G>T	p.Val46Leu	missense_variant	Exon 2 of 16		NP_001269221.1
ABCB8	NM_001282293.2	c.145-628G>T		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.136G>T	p.Val46Leu	missense_variant	Exon 2 of 16	1	NM_007188.5	ENSP00000351717.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449060 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 719098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.075
DANN	Benign	0.67
DEOGEN2	Benign	0.073	.;.;T;.;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.74	T;T;T;T;T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.043	T;T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.95	.;.;L;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.15	T;T;T;T;T;T
Sift4G	Benign	0.45	T;T;T;T;T;T
Polyphen		0.0, 0.0010	.;B;B;.;.;B
Vest4		0.070, 0.078, 0.11, 0.11, 0.099
MutPred		0.35		.;.;Gain of helix (P = 0.0022);.;.;.;
MVP		0.39
MPC		0.22
ClinPred		0.050	T
GERP RS		-6.7
Varity_R		0.034
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs566864336; hg19: chr7-150730732;