7-151033625-G-A

Position:

• chr7-151033625-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007188.5(ABCB8):​c.116G>A​(p.Ser39Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,587,502 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (168 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (143 hom.)
• Consequence: ABCB8 NM_007188.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.36

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024946928).
• BP6: Variant 7-151033625-G-A is Benign according to our data. Variant chr7-151033625-G-A is described in ClinVar as [Benign]. Clinvar id is 769736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB8	NM_007188.5	c.116G>A	p.Ser39Asn	missense_variant	2/16	ENST00000358849.9
ABCB8	NM_001282291.2	c.167G>A	p.Ser56Asn	missense_variant	3/17
ABCB8	NM_001282292.2	c.116G>A	p.Ser39Asn	missense_variant	2/16
ABCB8	NM_001282293.2	c.145-648G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB8	ENST00000358849.9	c.116G>A	p.Ser39Asn	missense_variant	2/16	1	NM_007188.5	P1

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3804 AN: 152132 Hom.: 167 Cov.: 33

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000956

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.00748 AC: 1743 AN: 232934 Hom.: 56 AF XY: 0.00570 AC XY: 718 AN XY: 126000

Gnomad AFR exome AF: 0.0861

Gnomad AMR exome AF: 0.00620

Gnomad ASJ exome AF: 0.00403

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000250

Gnomad FIN exome AF: 0.0000484

Gnomad NFE exome AF: 0.00104

Gnomad OTH exome AF: 0.00427

GnomAD4 exome AF: 0.00314 AC: 4508 AN: 1435252 Hom.: 143 Cov.: 30 AF XY: 0.00282 AC XY: 2001 AN XY: 710686

Gnomad4 AFR exome AF: 0.0870

Gnomad4 AMR exome AF: 0.00659

Gnomad4 ASJ exome AF: 0.00337

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000287

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.000665

Gnomad4 OTH exome AF: 0.00784

GnomAD4 genome AF: 0.0251 AC: 3818 AN: 152250 Hom.: 168 Cov.: 33 AF XY: 0.0243 AC XY: 1808 AN XY: 74438

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000956

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.00582 Hom.: 65

Bravo AF: 0.0293

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0772 AC: 340

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.00874 AC: 1061

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	.;.;T;.;.;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.61	T;T;T;T;T;T
MetaRNN	Benign	0.0025	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;.;L;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	N;N;N;N;N;N
REVEL	Benign	0.085
Sift	Uncertain	0.0030	D;D;D;D;D;D
Sift4G	Uncertain	0.023	D;T;T;T;D;D
Polyphen		0.28, 0.36	.;B;B;.;.;B
Vest4		0.14, 0.16, 0.23, 0.13, 0.17
MVP		0.89
MPC		0.21
ClinPred		0.029	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.044
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs6975981; hg19: chr7-150730712;