rs3774907

Variant names:

• chr4-23828239-G-A
• rs3774907
• NM_013261.5:c.757+161C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-23828239-G-A
• chr4-23828239-G-C
• chr4-23828239-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.757+161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,108 control chromosomes in the GnomAD database, including 49,535 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 0.81 (49535 hom., cov: 31)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_013261.5	MANE Select	c.757+161C>T		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.772+161C>T		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.772+161C>T		intron	N/A	NP_001341754.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.757+161C>T		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.376+161C>T		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.757+161C>T		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122444 AN: 151990 Hom.: 49488 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.806 AC: 122548 AN: 152108 Hom.: 49535 Cov.: 31 AF XY: 0.808 AC XY: 60114 AN XY: 74360

African (AFR) AF: 0.855 AC: 35481 AN: 41506

American (AMR) AF: 0.850 AC: 12980 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2840 AN: 3470

East Asian (EAS) AF: 0.769 AC: 3960 AN: 5152

South Asian (SAS) AF: 0.752 AC: 3623 AN: 4816

European-Finnish (FIN) AF: 0.814 AC: 8627 AN: 10592

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52405 AN: 67974

Other (OTH) AF: 0.813 AC: 1718 AN: 2114

Alfa AF: 0.791 Hom.: 5807

Bravo AF: 0.811

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.78
DANN	Benign	0.63
PhyloP100		0.047
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: rs3774907; hg19: chr4-23829862;