1-46673908-C-G

Position:

• chr1-46673908-C-G

Variant summary

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

The 1-46673908-C-G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 158,430 control chromosomes in the GnomAD database, including 50,525 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 0.80 (48606 hom., cov: 33)
  • Exomes 𝑓: 0.79 (1919 hom.)
• Consequence: ATPAF1 ENST00000525633.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

Genes affected

ATPAF1 (HGNC:18803): (ATP synthase mitochondrial F1 complex assembly factor 1) This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 beta subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATPAF1	ENST00000525633.1			upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121367 AN: 152162 Hom.: 48533 Cov.: 33

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.820

GnomAD4 exome AF: 0.786 AC: 4834 AN: 6150 Hom.: 1919 Cov.: 0 AF XY: 0.785 AC XY: 2438 AN XY: 3104

Gnomad4 AFR exome AF: 0.823

Gnomad4 AMR exome AF: 0.854

Gnomad4 ASJ exome AF: 0.791

Gnomad4 EAS exome AF: 0.939

Gnomad4 SAS exome AF: 0.719

Gnomad4 FIN exome AF: 0.787

Gnomad4 NFE exome AF: 0.766

Gnomad4 OTH exome AF: 0.820

GnomAD4 genome AF: 0.798 AC: 121497 AN: 152280 Hom.: 48606 Cov.: 33 AF XY: 0.801 AC XY: 59618 AN XY: 74464

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.823

Alfa AF: 0.736 Hom.: 2507

Bravo AF: 0.806

Asia WGS AF: 0.820 AC: 2853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs601060; hg19: chr1-47139580;