rs1040436

Variant names:

• chr6-35400132-A-G
• rs1040436
• NM_006238.5:c.-101-10855A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-35400132-A-G
• chr6-35400132-A-T

Variant summary

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

The NM_006238.5(PPARD):​c.-101-10855A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,074 control chromosomes in the GnomAD database, including 35,075 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 0.66 (35075 hom., cov: 31)
• Consequence: PPARD NM_006238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 11 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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5	c.-101-10855A>G		intron_variant	Intron 2 of 7	ENST00000360694.8	NP_006229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARD	ENST00000360694.8	c.-101-10855A>G		intron_variant	Intron 2 of 7	2	NM_006238.5	ENSP00000353916.3

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99639 AN: 151956 Hom.: 35060 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.655 AC: 99677 AN: 152074 Hom.: 35075 Cov.: 31 AF XY: 0.663 AC XY: 49281 AN XY: 74348

African (AFR) AF: 0.385 AC: 15972 AN: 41474

American (AMR) AF: 0.719 AC: 10978 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1981 AN: 3472

East Asian (EAS) AF: 0.715 AC: 3683 AN: 5154

South Asian (SAS) AF: 0.787 AC: 3794 AN: 4822

European-Finnish (FIN) AF: 0.865 AC: 9166 AN: 10600

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51877 AN: 67962

Other (OTH) AF: 0.646 AC: 1365 AN: 2114

Alfa AF: 0.716 Hom.: 50833

Bravo AF: 0.631

Asia WGS AF: 0.706 AC: 2451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.6
DANN	Benign	0.83
PhyloP100		-0.15
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: rs1040436; hg19: chr6-35367909;