4-23873936-G-A

Variant names:

• chr4-23873936-G-A
• rs4550905
• NM_013261.5:c.234+10816C>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+10816C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,044 control chromosomes in the GnomAD database, including 30,478 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 (30478 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 8 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 (NFE) 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_013261.5	MANE Select	c.234+10816C>T		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.249+10816C>T		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.249+10816C>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+10816C>T		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.-148+6793C>T		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.234+10816C>T		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95313 AN: 151924 Hom.: 30487 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.627 AC: 95333 AN: 152044 Hom.: 30478 Cov.: 32 AF XY: 0.626 AC XY: 46486 AN XY: 74306

African (AFR) AF: 0.502 AC: 20786 AN: 41446

American (AMR) AF: 0.578 AC: 8822 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2165 AN: 3470

East Asian (EAS) AF: 0.653 AC: 3380 AN: 5176

South Asian (SAS) AF: 0.670 AC: 3224 AN: 4814

European-Finnish (FIN) AF: 0.693 AC: 7325 AN: 10566

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47519 AN: 67990

Other (OTH) AF: 0.628 AC: 1323 AN: 2106

Alfa AF: 0.679 Hom.: 20627

Bravo AF: 0.612

Asia WGS AF: 0.652 AC: 2266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		0.53
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: rs4550905; hg19: chr4-23875559;