NM_013261.5:c.54+945A>G

Variant names:

• chr4-23888959-T-C
• rs2970871
• NM_013261.5:c.54+945A>G

Variant summary

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

The NM_013261.5(PPARGC1A):​c.54+945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 984,754 control chromosomes in the GnomAD database, including 159,756 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 0.59 (26913 hom., cov: 31)
  • Exomes 𝑓: 0.56 (132843 hom.)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 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.54+945A>G		intron	N/A	NP_037393.1	Q9UBK2-1
	PPARGC1A	NM_001330751.2		c.70-4028A>G		intron	N/A	NP_001317680.1	Q9UBK2-3
	PPARGC1A	NM_001354825.2		c.70-4028A>G		intron	N/A	NP_001341754.1	Q9UBK2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.54+945A>G		intron	N/A	ENSP00000264867.2	Q9UBK2-1
	PPARGC1A	ENST00000506055.5	TSL:1	n.54+945A>G		intron	N/A	ENSP00000423075.1	Q9UBK2-2
	PPARGC1A	ENST00000513205.5	TSL:1	n.54+945A>G		intron	N/A	ENSP00000421632.1	Q9UBK2-8

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89431 AN: 151790 Hom.: 26880 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.610

GnomAD4 exome AF: 0.564 AC: 469709 AN: 832846 Hom.: 132843 Cov.: 32 AF XY: 0.564 AC XY: 217020 AN XY: 384620

African (AFR) AF: 0.721 AC: 11371 AN: 15780

American (AMR) AF: 0.529 AC: 521 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 3129 AN: 5152

East Asian (EAS) AF: 0.603 AC: 2190 AN: 3630

South Asian (SAS) AF: 0.559 AC: 9200 AN: 16456

European-Finnish (FIN) AF: 0.478 AC: 132 AN: 276

Middle Eastern (MID) AF: 0.664 AC: 1076 AN: 1620

European-Non Finnish (NFE) AF: 0.559 AC: 426138 AN: 761664

Other (OTH) AF: 0.585 AC: 15952 AN: 27284

GnomAD4 genome AF: 0.589 AC: 89506 AN: 151908 Hom.: 26913 Cov.: 31 AF XY: 0.583 AC XY: 43278 AN XY: 74242

African (AFR) AF: 0.700 AC: 29004 AN: 41412

American (AMR) AF: 0.567 AC: 8650 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2131 AN: 3470

East Asian (EAS) AF: 0.583 AC: 2994 AN: 5134

South Asian (SAS) AF: 0.578 AC: 2779 AN: 4810

European-Finnish (FIN) AF: 0.406 AC: 4283 AN: 10538

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37671 AN: 67968

Other (OTH) AF: 0.606 AC: 1278 AN: 2108

Alfa AF: 0.591 Hom.: 12872

Bravo AF: 0.610

Asia WGS AF: 0.577 AC: 2008 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.70
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2970871; hg19: chr4-23890582;