rs3768026

Positions:

• chr1-42661095-C-A
• chr1-42661095-C-T

Variant summary

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

The ENST00000304979.8(PPIH):​c.243+191C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 560,250 control chromosomes in the GnomAD database, including 28,881 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 0.31 (7450 hom., cov: 32)
  • Exomes 𝑓: 0.31 (21431 hom.)
• Consequence: PPIH ENST00000304979.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

PPIH (HGNC:14651): (peptidylprolyl isomerase H) The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein is a specific component of the complex that includes pre-mRNA processing factors PRPF3, PRPF4, and PRPF18, as well as U4/U5/U6 tri-snRNP. This protein has been shown to possess PPIase activity and may act as a protein chaperone that mediates the interactions between different proteins inside the spliceosome. [provided by RefSeq, Jul 2008]

(HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIH	NM_006347.4	c.243+191C>A		intron_variant		ENST00000304979.8	NP_006338.1
LOC124904162	XR_007066034.1	n.76+14625G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIH	ENST00000304979.8	c.243+191C>A		intron_variant		1	NM_006347.4	ENSP00000306614	P1
	ENST00000649886.1	n.1101+1204G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47143 AN: 151886 Hom.: 7448 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.315 AC: 128399 AN: 408246 Hom.: 21431 AF XY: 0.315 AC XY: 68196 AN XY: 216420

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.0964

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.310 AC: 47154 AN: 152004 Hom.: 7450 Cov.: 32 AF XY: 0.315 AC XY: 23364 AN XY: 74278

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.307

Alfa AF: 0.215 Hom.: 496

Bravo AF: 0.299

Asia WGS AF: 0.214 AC: 747 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	5.7
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs3768026; hg19: chr1-43126766;