chr7-151034544-G-C

Variant names:

• chr7-151034544-G-C
• rs374410550
• NM_007188.5:c.604G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007188.5(ABCB8):​c.604G>C​(p.Val202Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V202I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ABCB8 NM_007188.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33510733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB8	NM_007188.5	c.604G>C	p.Val202Leu	missense_variant	Exon 4 of 16	ENST00000358849.9	NP_009119.2
ABCB8	NM_001282291.2	c.655G>C	p.Val219Leu	missense_variant	Exon 5 of 17		NP_001269220.1
ABCB8	NM_001282292.2	c.604G>C	p.Val202Leu	missense_variant	Exon 4 of 16		NP_001269221.1
ABCB8	NM_001282293.2	c.340G>C	p.Val114Leu	missense_variant	Exon 3 of 15		NP_001269222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB8	ENST00000358849.9	c.604G>C	p.Val202Leu	missense_variant	Exon 4 of 16	1	NM_007188.5	ENSP00000351717.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461190 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 726926

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	10
DANN	Benign	0.95
DEOGEN2	Benign	0.23	.;.;T;.;.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.83	T;T;T;T;D;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.78	.;.;N;.;.;.
PhyloP100		1.9
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.18	T;T;T;T;T;T
Sift4G	Benign	0.26	T;T;T;T;T;T
Polyphen		0.0010, 0.0020, 0.0030	.;B;B;.;.;B
Vest4		0.32
MutPred		0.49		.;.;Loss of catalytic residue at V219 (P = 0.0412);.;.;.;
MVP		0.88
MPC		0.22
ClinPred		0.22	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.64
Mutation Taster		=71/29	polymorphism

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: rs374410550; hg19: chr7-150731631;