rs11934028

Positions:

• chr4-23779306-C-A
• chr4-23779306-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_925475.3(LOC105374527):​n.44-113C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,792 control chromosomes in the GnomAD database, including 1,672 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 0.12 (1672 hom., cov: 31)
• Consequence: LOC105374527 XR_925475.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

Genes affected

LOC105374527 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105374527	XR_925475.3	n.44-113C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000509702.5	n.2434-14093G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17573 AN: 151674 Hom.: 1662 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.0718

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.116 AC: 17622 AN: 151792 Hom.: 1672 Cov.: 31 AF XY: 0.120 AC XY: 8908 AN XY: 74156

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.0714

Gnomad4 FIN AF: 0.0966

Gnomad4 NFE AF: 0.0372

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0263 Hom.: 15

Bravo AF: 0.129

Asia WGS AF: 0.147 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.29
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11934028; hg19: chr4-23780929;