rs12040764

Variant names:

• chr1-111458957-T-C
• rs12040764
• NM_001688.5:c.514-500T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-111458957-T-C
• chr1-111458957-T-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.514-500T>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 NM_001688.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 9 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=-0.98).
• 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 rank	MANE	Protein	UniProt
ATP5PB	NM_001688.5	c.514-500T>C		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.514-500T>C		intron_variant	Intron 5 of 6	1	NM_001688.5	ENSP00000358737.3
ATP5PB	ENST00000483994.1	c.331-500T>C		intron_variant	Intron 3 of 4	2		ENSP00000420366.1
ATP5PB	ENST00000369721.8	n.445-500T>C		intron_variant	Intron 4 of 5	2
ATP5PB	ENST00000468818.1	n.284-500T>C		intron_variant	Intron 4 of 5	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

African (AFR) AF: 0.545 AC: 22581 AN: 41414

American (AMR) AF: 0.227 AC: 3464 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 713 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1545 AN: 5166

South Asian (SAS) AF: 0.403 AC: 1939 AN: 4808

European-Finnish (FIN) AF: 0.312 AC: 3289 AN: 10556

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22463 AN: 67948

Other (OTH) AF: 0.333 AC: 702 AN: 2110

Alfa AF: 0.317 Hom.: 10979

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
PhyloP100		-1.1
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: rs12040764; hg19: chr1-112001579;