rs17576576

Positions:

• chr4-23906104-A-G

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.70-21173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,054 control chromosomes in the GnomAD database, including 9,117 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 0.33 (9117 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441

Genes affected

PPARGC1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_001330751.2	c.70-21173T>C		intron_variant
PPARGC1A	NM_001330752.2	c.19-21173T>C		intron_variant
PPARGC1A	NM_001354825.2	c.70-21173T>C		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50865 AN: 151936 Hom.: 9113 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.335 AC: 50898 AN: 152054 Hom.: 9117 Cov.: 32 AF XY: 0.330 AC XY: 24547 AN XY: 74328

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.0253

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.331

Alfa AF: 0.368 Hom.: 10879

Bravo AF: 0.317

Asia WGS AF: 0.146 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.1
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17576576; hg19: chr4-23907727;