4-23855828-T-G

Variant names:

• chr4-23855828-T-G
• rs7657517
• NM_013261.5:c.235-24077A>C

Variant summary

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

The ENST00000264867.7(PPARGC1A):​c.235-24077A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 151,944 control chromosomes in the GnomAD database, including 7,179 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 0.26 (7179 hom., cov: 32)
• Consequence: PPARGC1A ENST00000264867.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 5 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 = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264867.7. 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.235-24077A>C		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.250-24077A>C		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.250-24077A>C		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.235-24077A>C		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.-147-24077A>C		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.235-24077A>C		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38681 AN: 151826 Hom.: 7162 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.255 AC: 38746 AN: 151944 Hom.: 7179 Cov.: 32 AF XY: 0.252 AC XY: 18751 AN XY: 74282

African (AFR) AF: 0.528 AC: 21851 AN: 41374

American (AMR) AF: 0.222 AC: 3393 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3472

East Asian (EAS) AF: 0.175 AC: 905 AN: 5158

South Asian (SAS) AF: 0.174 AC: 837 AN: 4814

European-Finnish (FIN) AF: 0.129 AC: 1363 AN: 10582

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9182 AN: 67966

Other (OTH) AF: 0.233 AC: 491 AN: 2108

Alfa AF: 0.0503 Hom.: 60

Bravo AF: 0.276

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.82
PhyloP100		-0.035
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: rs7657517; hg19: chr4-23857451;