rs9658134

Variant names:

• chr6-35411021-G-T
• rs9658134
• NM_006238.5:c.-67G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-35411021-G-T
• chr6-35411021-G-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006238.5(PPARD):​c.-67G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,383,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: PPARD NM_006238.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 7 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BS2: High AC in GnomAd4 at 18 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006238.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARD	NM_006238.5	MANE Select	c.-67G>T		5_prime_UTR	Exon 3 of 8	NP_006229.1	Q03181-1
	PPARD	NM_001171818.2		c.-67G>T		5_prime_UTR	Exon 4 of 9	NP_001165289.1	Q03181-1
	PPARD	NM_177435.3		c.-67G>T		5_prime_UTR	Exon 3 of 7	NP_803184.1	Q03181-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARD	ENST00000360694.8	TSL:2 MANE Select	c.-67G>T		5_prime_UTR	Exon 3 of 8	ENSP00000353916.3	Q03181-1
	PPARD	ENST00000311565.4	TSL:5	c.-67G>T		5_prime_UTR	Exon 4 of 9	ENSP00000310928.4	Q03181-1
	PPARD	ENST00000875334.1		c.-67G>T		5_prime_UTR	Exon 2 of 7	ENSP00000545393.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 124 AN: 1230996 Hom.: 0 Cov.: 33 AF XY: 0.0000886 AC XY: 53 AN XY: 598484

African (AFR) AF: 0.0000386 AC: 1 AN: 25932

American (AMR) AF: 0.00 AC: 0 AN: 17420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16418

East Asian (EAS) AF: 0.00 AC: 0 AN: 31330

South Asian (SAS) AF: 0.00 AC: 0 AN: 48818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4862

European-Non Finnish (NFE) AF: 0.000118 AC: 117 AN: 991190

Other (OTH) AF: 0.000121 AC: 6 AN: 49676

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74298

African (AFR) AF: 0.0000966 AC: 4 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 42

Bravo AF: 0.0000982

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.9
DANN	Benign	0.79
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs9658134; hg19: chr6-35378798;