rs12040764

Positions:

• chr1-111458957-T-C
• chr1-111458957-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369722.8(ATP5PB):​c.514-500T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,968 control chromosomes in the GnomAD database, including 11,733 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 0.38 (11733 hom., cov: 32)
• Consequence: ATP5PB ENST00000369722.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP5PB	NM_001688.5	c.514-500T>C		intron_variant		ENST00000369722.8	NP_001679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP5PB	ENST00000369722.8	c.514-500T>C		intron_variant		1	NM_001688.5	ENSP00000358737	P1
ATP5PB	ENST00000483994.1	c.331-500T>C		intron_variant		2		ENSP00000420366
ATP5PB	ENST00000369721.8	n.445-500T>C		intron_variant, non_coding_transcript_variant		2
ATP5PB	ENST00000468818.1	n.284-500T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56982 AN: 151850 Hom.: 11724 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.375 AC: 57036 AN: 151968 Hom.: 11733 Cov.: 32 AF XY: 0.374 AC XY: 27813 AN XY: 74270

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.333

Alfa AF: 0.313 Hom.: 9143

Bravo AF: 0.368

Asia WGS AF: 0.335 AC: 1168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.59
DANN	Benign	0.45

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: rs12040764; hg19: chr1-112001579;