rs3796407

Variant names:

• chr4-23883088-G-A
• rs3796407
• NM_013261.5:c.234+1664C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013261.5(PPARGC1A):​c.234+1664C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,168 control chromosomes in the GnomAD database, including 3,612 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 0.19 (3612 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+1664C>T		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+1664C>T		intron_variant	Intron 2 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29432 AN: 152046 Hom.: 3615 Cov.: 32

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.0860

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.193 AC: 29417 AN: 152164 Hom.: 3612 Cov.: 32 AF XY: 0.187 AC XY: 13940 AN XY: 74402

African (AFR) AF: 0.0663 AC: 2754 AN: 41544

American (AMR) AF: 0.191 AC: 2919 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1132 AN: 3470

East Asian (EAS) AF: 0.0853 AC: 441 AN: 5172

South Asian (SAS) AF: 0.122 AC: 589 AN: 4822

European-Finnish (FIN) AF: 0.169 AC: 1787 AN: 10594

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18875 AN: 67968

Other (OTH) AF: 0.225 AC: 475 AN: 2112

Alfa AF: 0.253 Hom.: 7121

Bravo AF: 0.194

Asia WGS AF: 0.0870 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.91
PhyloP100		2.8
Mutation Taster		=99/1	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: rs3796407; hg19: chr4-23884711;