1-42661095-C-A

Variant names:

• chr1-42661095-C-A
• rs3768026
• NM_006347.4:c.243+191C>A

Variant summary

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

The NM_006347.4(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 NM_006347.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 1 publications found

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]

ENSG00000285728 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006347.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIH	NM_006347.4	MANE Select	c.243+191C>A		intron	N/A	NP_006338.1
	PPIH	NM_001330510.2		c.114+191C>A		intron	N/A	NP_001317439.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIH	ENST00000304979.8	TSL:1 MANE Select	c.243+191C>A		intron	N/A	ENSP00000306614.3
	PPIH	ENST00000372550.6	TSL:1	c.243+191C>A		intron	N/A	ENSP00000361630.2
	PPIH	ENST00000676675.1		c.243+191C>A		intron	N/A	ENSP00000503489.1

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

African (AFR) AF: 0.284 AC: 2958 AN: 10408

American (AMR) AF: 0.297 AC: 4108 AN: 13816

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 3620 AN: 12460

East Asian (EAS) AF: 0.0964 AC: 2669 AN: 27692

South Asian (SAS) AF: 0.333 AC: 12563 AN: 37672

European-Finnish (FIN) AF: 0.410 AC: 12272 AN: 29906

Middle Eastern (MID) AF: 0.307 AC: 1068 AN: 3484

European-Non Finnish (NFE) AF: 0.328 AC: 81766 AN: 248914

Other (OTH) AF: 0.309 AC: 7375 AN: 23894

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

African (AFR) AF: 0.287 AC: 11894 AN: 41434

American (AMR) AF: 0.299 AC: 4571 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 966 AN: 3470

East Asian (EAS) AF: 0.141 AC: 729 AN: 5168

South Asian (SAS) AF: 0.315 AC: 1518 AN: 4820

European-Finnish (FIN) AF: 0.411 AC: 4331 AN: 10548

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22264 AN: 67970

Other (OTH) AF: 0.307 AC: 648 AN: 2112

Alfa AF: 0.218 Hom.: 527

Bravo AF: 0.299

Asia WGS AF: 0.214 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.69
PhyloP100		1.1
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: rs3768026; hg19: chr1-43126766;