rs10489100

Positions:

• chr4-24079823-C-G
• chr4-24079823-C-T

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.69+11645G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 152,050 control chromosomes in the GnomAD database, including 610 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 0.085 (610 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191

Genes affected

PPARGC1A (HGNC:):

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 = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_001330751.2	c.69+11645G>C		intron_variant
PPARGC1A	NM_001330752.2	c.18+178380G>C		intron_variant
PPARGC1A	NM_001354825.2	c.69+11645G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12830 AN: 151932 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0874

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0722

Gnomad OTH AF: 0.0808

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

GnomAD4 genome AF: 0.0845 AC: 12853 AN: 152050 Hom.: 610 Cov.: 32 AF XY: 0.0830 AC XY: 6169 AN XY: 74324

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.0874

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0263

Gnomad4 NFE AF: 0.0722

Gnomad4 OTH AF: 0.0828

Alfa AF: 0.0307 Hom.: 24

Bravo AF: 0.0867

Asia WGS AF: 0.135 AC: 467 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10489100; hg19: chr4-24081446;