4-24053802-T-G

Variant summary

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

The NM_001330751.2(PPARGC1A):c.69+37666A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 151,940 control chromosomes in the GnomAD database, including 29,529 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 0.62 (29529 hom., cov: 31)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479

Genes affected

PPARGC1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_001330751.2	c.69+37666A>C		intron_variant
PPARGC1A	NM_001330752.2	c.19-168871A>C		intron_variant
PPARGC1A	NM_001354825.2	c.69+37666A>C		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94416 AN: 151820 Hom.: 29507 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.622 AC: 94486 AN: 151940 Hom.: 29529 Cov.: 31 AF XY: 0.618 AC XY: 45894 AN XY: 74260

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.626

Alfa AF: 0.631 Hom.: 13368

Bravo AF: 0.615

Asia WGS AF: 0.552 AC: 1922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.4
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: rs614457; hg19: chr4-24055425;