chr1-111450602-C-T

Variant names:

• chr1-111450602-C-T
• rs1264897
• NM_001688.5:c.77+729C>T

Variant summary

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

The NM_001688.5(ATP5PB):​c.77+729C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,050 control chromosomes in the GnomAD database, including 19,565 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 0.49 (19565 hom., cov: 32)
• Consequence: ATP5PB NM_001688.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• Publications: 18 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5PB	NM_001688.5	c.77+729C>T		intron_variant	Intron 2 of 6	ENST00000369722.8	NP_001679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5PB	ENST00000369722.8	c.77+729C>T		intron_variant	Intron 2 of 6	1	NM_001688.5	ENSP00000358737.3

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74443 AN: 151932 Hom.: 19536 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.490 AC: 74526 AN: 152050 Hom.: 19565 Cov.: 32 AF XY: 0.495 AC XY: 36777 AN XY: 74308

African (AFR) AF: 0.657 AC: 27262 AN: 41482

American (AMR) AF: 0.334 AC: 5112 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3468

East Asian (EAS) AF: 0.744 AC: 3853 AN: 5178

South Asian (SAS) AF: 0.615 AC: 2965 AN: 4820

European-Finnish (FIN) AF: 0.453 AC: 4771 AN: 10528

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.414 AC: 28171 AN: 67974

Other (OTH) AF: 0.457 AC: 966 AN: 2112

Alfa AF: 0.430 Hom.: 8208

Bravo AF: 0.483

Asia WGS AF: 0.619 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.0
DANN	Benign	0.48
PhyloP100		-0.10
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: rs1264897; hg19: chr1-111993224;