rs16874276

Variant names:

• chr4-23880354-G-A
• rs16874276
• NM_013261.5:c.234+4398C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-23880354-G-A
• chr4-23880354-G-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+4398C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,040 control chromosomes in the GnomAD database, including 413 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 0.070 (413 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0832 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013261.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_013261.5	MANE Select	c.234+4398C>T		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.249+4398C>T		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.249+4398C>T		intron	N/A	NP_001341754.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.234+4398C>T		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.-148+375C>T		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.234+4398C>T		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10659 AN: 151922 Hom.: 412 Cov.: 33

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0559

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.0593

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.0609

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0702 AC: 10674 AN: 152040 Hom.: 413 Cov.: 33 AF XY: 0.0679 AC XY: 5047 AN XY: 74316

African (AFR) AF: 0.0856 AC: 3547 AN: 41456

American (AMR) AF: 0.0559 AC: 853 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0779 AC: 270 AN: 3466

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5164

South Asian (SAS) AF: 0.0595 AC: 287 AN: 4820

European-Finnish (FIN) AF: 0.0372 AC: 393 AN: 10570

Middle Eastern (MID) AF: 0.0621 AC: 18 AN: 290

European-Non Finnish (NFE) AF: 0.0747 AC: 5079 AN: 67980

Other (OTH) AF: 0.0739 AC: 156 AN: 2112

Alfa AF: 0.0704 Hom.: 720

Bravo AF: 0.0708

Asia WGS AF: 0.0300 AC: 106 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.045
DANN	Benign	0.31
PhyloP100		-1.3
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: rs16874276; hg19: chr4-23881977; COSMIC: COSV53527461; COSMIC: COSV53527461;