rs6448228

Variant names:

• chr4-23860519-A-G
• rs6448228
• NM_013261.5:c.234+24233T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-23860519-A-G
• chr4-23860519-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013261.5(PPARGC1A):​c.234+24233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,962 control chromosomes in the GnomAD database, including 12,160 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 0.40 (12160 hom., cov: 31)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• Publications: 6 publications found

Genes affected

PPARGC1A (HGNC:9237): (PPARG coactivator 1 alpha) The protein encoded by this gene is a transcriptional coactivator that regulates the genes involved in energy metabolism. This protein interacts with PPARgamma, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activities of, cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+24233T>C		intron_variant	Intron 2 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.234+24233T>C		intron_variant	Intron 2 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60653 AN: 151844 Hom.: 12137 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.400 AC: 60719 AN: 151962 Hom.: 12160 Cov.: 31 AF XY: 0.401 AC XY: 29792 AN XY: 74270

African (AFR) AF: 0.374 AC: 15508 AN: 41426

American (AMR) AF: 0.390 AC: 5952 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1662 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2244 AN: 5156

South Asian (SAS) AF: 0.446 AC: 2146 AN: 4814

European-Finnish (FIN) AF: 0.382 AC: 4031 AN: 10542

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27568 AN: 67964

Other (OTH) AF: 0.412 AC: 870 AN: 2114

Alfa AF: 0.399 Hom.: 1759

Bravo AF: 0.398

Asia WGS AF: 0.465 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.41
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6448228; hg19: chr4-23862142;