4-24172160-A-T

Position:

• chr4-24172160-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.-99-80525T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 152,148 control chromosomes in the GnomAD database, including 53,658 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 0.83 (53658 hom., cov: 31)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

Genes affected

PPARGC1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.-99-80525T>A		intron_variant			NP_001317680.1
PPARGC1A	NM_001330752.2	c.18+86043T>A		intron_variant			NP_001317681.1
PPARGC1A	NM_001354825.2	c.-99-80525T>A		intron_variant			NP_001341754.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126147 AN: 152030 Hom.: 53621 Cov.: 31

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.944

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.830 AC: 126242 AN: 152148 Hom.: 53658 Cov.: 31 AF XY: 0.835 AC XY: 62123 AN XY: 74394

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.944

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.909

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.909

Gnomad4 OTH AF: 0.848

Alfa AF: 0.874 Hom.: 6893

Bravo AF: 0.815

Asia WGS AF: 0.889 AC: 3089 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4697438; hg19: chr4-24173783;