rs16874486

chr4-23989477-T-C

Variant summary

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

The NM_001330751.2(PPARGC1A):c.69+101991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 151,826 control chromosomes in the GnomAD database, including 2,516 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 0.15 (2516 hom., cov: 31)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

Genes affected

PPARGC1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_001330751.2	c.69+101991A>G		intron_variant
PPARGC1A	NM_001330752.2	c.19-104546A>G		intron_variant
PPARGC1A	NM_001354825.2	c.69+101991A>G		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23056 AN: 151708 Hom.: 2505 Cov.: 31

Gnomad AFR AF: 0.0384

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.152 AC: 23068 AN: 151826 Hom.: 2516 Cov.: 31 AF XY: 0.158 AC XY: 11712 AN XY: 74200

Gnomad4 AFR AF: 0.0383

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.140

Alfa AF: 0.168 Hom.: 3220

Bravo AF: 0.157

Asia WGS AF: 0.185 AC: 640 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.6
Dann	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16874486; hg19: chr4-23991100;