NM_013261.5:c.234+11456A>T

Variant names:

• chr4-23873296-T-A
• rs13106578
• NM_013261.5:c.234+11456A>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+11456A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 149,660 control chromosomes in the GnomAD database, including 30,097 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 0.63 (30097 hom., cov: 28)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 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+11456A>T		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.249+11456A>T		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.249+11456A>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+11456A>T		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.-148+7433A>T		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.234+11456A>T		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 93894 AN: 149544 Hom.: 30107 Cov.: 28

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.628 AC: 93913 AN: 149660 Hom.: 30097 Cov.: 28 AF XY: 0.625 AC XY: 45580 AN XY: 72944

African (AFR) AF: 0.510 AC: 20729 AN: 40606

American (AMR) AF: 0.579 AC: 8686 AN: 15008

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2177 AN: 3450

East Asian (EAS) AF: 0.671 AC: 3425 AN: 5104

South Asian (SAS) AF: 0.642 AC: 3036 AN: 4728

European-Finnish (FIN) AF: 0.684 AC: 6888 AN: 10064

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.695 AC: 46885 AN: 67420

Other (OTH) AF: 0.634 AC: 1321 AN: 2084

Alfa AF: 0.648 Hom.: 4016

Bravo AF: 0.615

Asia WGS AF: 0.650 AC: 2262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.016
DANN	Benign	0.38
PhyloP100		-1.9
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: rs13106578; hg19: chr4-23874919;