rs640050

Positions:

• chr4-24046063-A-G
• chr4-24046063-A-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+45405T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,014 control chromosomes in the GnomAD database, including 21,313 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 0.52 (21313 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680

Genes affected

PPARGC1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_001330751.2	c.69+45405T>C		intron_variant
PPARGC1A	NM_001330752.2	c.19-161132T>C		intron_variant
PPARGC1A	NM_001354825.2	c.69+45405T>C		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79296 AN: 151896 Hom.: 21318 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.522 AC: 79318 AN: 152014 Hom.: 21313 Cov.: 32 AF XY: 0.520 AC XY: 38602 AN XY: 74274

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.524

Alfa AF: 0.570 Hom.: 15430

Bravo AF: 0.509

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.0
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs640050; hg19: chr4-24047686;