rs4697429

chr4-23935451-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001330751.2(PPARGC1A):c.70-50520A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,154 control chromosomes in the GnomAD database, including 3,973 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 0.20 (3973 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589

Genes affected

PPARGC1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_001330751.2	c.70-50520A>G		intron_variant
PPARGC1A	NM_001330752.2	c.19-50520A>G		intron_variant
PPARGC1A	NM_001354825.2	c.70-50520A>G		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30875 AN: 152036 Hom.: 3964 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.203 AC: 30891 AN: 152154 Hom.: 3973 Cov.: 32 AF XY: 0.209 AC XY: 15521 AN XY: 74368

Gnomad4 AFR AF: 0.0815

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.191

Alfa AF: 0.217 Hom.: 4725

Bravo AF: 0.209

Asia WGS AF: 0.257 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	5.9
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4697429; hg19: chr4-23937074; COSMIC: COSV67202840;