rs1891756

Positions:

• chr1-111458413-C-G
• chr1-111458413-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ATP5PB	NM_001688.5	c.514-1044C>G		intron_variant		ENST00000369722.8	NP_001679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP5PB	ENST00000369722.8	c.514-1044C>G		intron_variant		1	NM_001688.5	ENSP00000358737	P1
ATP5PB	ENST00000483994.1	c.331-1044C>G		intron_variant		2		ENSP00000420366
ATP5PB	ENST00000369721.8	n.445-1044C>G		intron_variant, non_coding_transcript_variant		2
ATP5PB	ENST00000468818.1	n.284-1044C>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.468

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

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: rs1891756; hg19: chr1-112001035;