chr1-111458413-C-G

Variant names:

• chr1-111458413-C-G
• rs1891756
• NM_001688.5:c.514-1044C>G

Variant summary

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

The NM_001688.5(ATP5PB):​c.514-1044C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,988 control chromosomes in the GnomAD database, including 20,885 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 0.50 (20885 hom., cov: 32)
• Consequence: ATP5PB NM_001688.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838
• Publications: 4 publications found

Genes affected

ATP5PB (HGNC:840): (ATP synthase peripheral stalk-membrane subunit b) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the b subunit of the proton channel. [provided by RefSeq, Jul 2008]

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 (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5PB	NM_001688.5	c.514-1044C>G		intron_variant	Intron 5 of 6	ENST00000369722.8	NP_001679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5PB	ENST00000369722.8	c.514-1044C>G		intron_variant	Intron 5 of 6	1	NM_001688.5	ENSP00000358737.3
ATP5PB	ENST00000483994.1	c.331-1044C>G		intron_variant	Intron 3 of 4	2		ENSP00000420366.1
ATP5PB	ENST00000369721.8	n.445-1044C>G		intron_variant	Intron 4 of 5	2
ATP5PB	ENST00000468818.1	n.284-1044C>G		intron_variant	Intron 4 of 5	3

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76342 AN: 151870 Hom.: 20853 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.470

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.503 AC: 76428 AN: 151988 Hom.: 20885 Cov.: 32 AF XY: 0.507 AC XY: 37692 AN XY: 74278

African (AFR) AF: 0.701 AC: 29038 AN: 41436

American (AMR) AF: 0.338 AC: 5168 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1041 AN: 3462

East Asian (EAS) AF: 0.743 AC: 3846 AN: 5176

South Asian (SAS) AF: 0.618 AC: 2979 AN: 4822

European-Finnish (FIN) AF: 0.454 AC: 4780 AN: 10524

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28188 AN: 67970

Other (OTH) AF: 0.468 AC: 987 AN: 2108

Alfa AF: 0.447 Hom.: 1990

Bravo AF: 0.497

Asia WGS AF: 0.621 AC: 2160 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	0.28
DANN	Benign	0.60
PhyloP100		-0.84
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: rs1891756; hg19: chr1-112001035;