19-9848880-C-T

Variant names:

• chr19-9848880-C-T
• rs4804461
• NM_006221.4:c.383-210C>T

Variant summary

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

The NM_006221.4(PIN1):​c.383-210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,112 control chromosomes in the GnomAD database, including 3,474 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 0.21 (3474 hom., cov: 33)
• Consequence: PIN1 NM_006221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 8 publications found

Genes affected

PIN1 (HGNC:8988): (peptidylprolyl cis/trans isomerase, NIMA-interacting 1) Peptidyl-prolyl cis/trans isomerases (PPIases) catalyze the cis/trans isomerization of peptidyl-prolyl peptide bonds. This gene encodes one of the PPIases, which specifically binds to phosphorylated ser/thr-pro motifs to catalytically regulate the post-phosphorylation conformation of its substrates. The conformational regulation catalyzed by this PPIase has a profound impact on key proteins involved in the regulation of cell growth, genotoxic and other stress responses, the immune response, induction and maintenance of pluripotency, germ cell development, neuronal differentiation, and survival. This enzyme also plays a key role in the pathogenesis of Alzheimer's disease and many cancers. Multiple alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jun 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006221.4. 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
	PIN1	NM_006221.4	MANE Select	c.383-210C>T		intron	N/A	NP_006212.1	Q13526
	PIN1	NR_038422.3		n.463-210C>T		intron	N/A
	PIN1	NR_038830.2		n.463-210C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN1	ENST00000247970.9	TSL:1 MANE Select	c.383-210C>T		intron	N/A	ENSP00000247970.5	Q13526
	PIN1	ENST00000380889.6	TSL:1	n.1416-210C>T		intron	N/A
	PIN1	ENST00000929406.1		c.428-210C>T		intron	N/A	ENSP00000599465.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31463 AN: 151994 Hom.: 3473 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0981

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.207 AC: 31475 AN: 152112 Hom.: 3474 Cov.: 33 AF XY: 0.202 AC XY: 15045 AN XY: 74360

African (AFR) AF: 0.162 AC: 6732 AN: 41512

American (AMR) AF: 0.168 AC: 2564 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3472

East Asian (EAS) AF: 0.0979 AC: 505 AN: 5158

South Asian (SAS) AF: 0.166 AC: 799 AN: 4826

European-Finnish (FIN) AF: 0.200 AC: 2118 AN: 10602

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.250 AC: 16959 AN: 67940

Other (OTH) AF: 0.222 AC: 469 AN: 2108

Alfa AF: 0.226 Hom.: 4414

Bravo AF: 0.202

Asia WGS AF: 0.120 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.80
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs4804461; hg19: chr19-9959556;