rs16875109

chr4-24138058-G-Achr4-24138058-G-C

Variant summary

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

The NM_001330751.2(PPARGC1A):c.-99-46423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,978 control chromosomes in the GnomAD database, including 7,872 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 0.31 (7872 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

Genes affected

PPARGC1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_001330751.2	c.-99-46423C>T		intron_variant
PPARGC1A	NM_001330752.2	c.18+120145C>T		intron_variant
PPARGC1A	NM_001354825.2	c.-99-46423C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46381 AN: 151860 Hom.: 7865 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.305 AC: 46422 AN: 151978 Hom.: 7872 Cov.: 32 AF XY: 0.308 AC XY: 22883 AN XY: 74302

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.281

Alfa AF: 0.263 Hom.: 719

Bravo AF: 0.318

Asia WGS AF: 0.310 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.6
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16875109; hg19: chr4-24139681;