rs2076168

Variant names:

• chr6-35422222-G-A
• rs2076168
• NM_006238.5:c.424+264G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-35422222-G-A
• chr6-35422222-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006238.5(PPARD):​c.424+264G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 152,128 control chromosomes in the GnomAD database, including 18 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 0.014 (18 hom., cov: 32)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 10 publications found

Genes affected

PPARD (HGNC:9235): (peroxisome proliferator activated receptor delta) This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. The encoded protein is thought to function as an integrator of transcriptional repression and nuclear receptor signaling. It may inhibit the ligand-induced transcriptional activity of peroxisome proliferator activated receptors alpha and gamma, though evidence for this effect is inconsistent. Expression of this gene in colorectal cancer cells may be variable but is typically relatively low. Knockout studies in mice suggested a role for this protein in myelination of the corpus callosum, lipid metabolism, differentiation, and epidermal cell proliferation. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0139 (2113/152128) while in subpopulation AMR AF = 0.0261 (399/15296). AF 95% confidence interval is 0.024. There are 18 homozygotes in GnomAd4. There are 1002 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.424+264G>A		intron_variant	Intron 5 of 7	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694.8	c.424+264G>A		intron_variant	Intron 5 of 7	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 2115 AN: 152010 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00796

Gnomad OTH AF: 0.0273

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

GnomAD4 genome AF: 0.0139 AC: 2113 AN: 152128 Hom.: 18 Cov.: 32 AF XY: 0.0135 AC XY: 1002 AN XY: 74394

African (AFR) AF: 0.0207 AC: 860 AN: 41458

American (AMR) AF: 0.0261 AC: 399 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4822

European-Finnish (FIN) AF: 0.000755 AC: 8 AN: 10600

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00794 AC: 540 AN: 67990

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

Alfa AF: 0.00150 Hom.: 2378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.8
DANN	Benign	0.93
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism

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: rs2076168; hg19: chr6-35389999;