NM_006221.4:c.382+62A>G

Variant names:

• chr19-9848202-A-G
• rs2010457
• NM_006221.4:c.382+62A>G

Variant summary

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

The NM_006221.4(PIN1):​c.382+62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,001,368 control chromosomes in the GnomAD database, including 53,890 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 0.33 (8492 hom., cov: 32)
  • Exomes 𝑓: 0.32 (45398 hom.)
• Consequence: PIN1 NM_006221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 12 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN1	NM_006221.4	MANE Select	c.382+62A>G		intron	N/A	NP_006212.1
	PIN1	NR_038422.3		n.462+62A>G		intron	N/A
	PIN1	NR_038830.2		n.462+62A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN1	ENST00000247970.9	TSL:1 MANE Select	c.382+62A>G		intron	N/A	ENSP00000247970.5
	PIN1	ENST00000380889.6	TSL:1	n.1415+62A>G		intron	N/A
	PIN1	ENST00000587625.5	TSL:2	c.*6A>G		3_prime_UTR	Exon 3 of 3	ENSP00000466656.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50314 AN: 151936 Hom.: 8487 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.313

GnomAD2 exomes AF: 0.318 AC: 65672 AN: 206720 AF XY: 0.327

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.271

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.320 AC: 271392 AN: 849314 Hom.: 45398 Cov.: 11 AF XY: 0.324 AC XY: 144169 AN XY: 444340

African (AFR) AF: 0.360 AC: 7851 AN: 21796

American (AMR) AF: 0.196 AC: 7775 AN: 39684

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 6527 AN: 21916

East Asian (EAS) AF: 0.267 AC: 9570 AN: 35896

South Asian (SAS) AF: 0.399 AC: 28755 AN: 72096

European-Finnish (FIN) AF: 0.334 AC: 16620 AN: 49792

Middle Eastern (MID) AF: 0.354 AC: 1543 AN: 4362

European-Non Finnish (NFE) AF: 0.319 AC: 179761 AN: 563598

Other (OTH) AF: 0.323 AC: 12990 AN: 40174

GnomAD4 genome AF: 0.331 AC: 50337 AN: 152054 Hom.: 8492 Cov.: 32 AF XY: 0.331 AC XY: 24622 AN XY: 74318

African (AFR) AF: 0.364 AC: 15090 AN: 41486

American (AMR) AF: 0.247 AC: 3768 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1391 AN: 5158

South Asian (SAS) AF: 0.395 AC: 1903 AN: 4822

European-Finnish (FIN) AF: 0.359 AC: 3801 AN: 10596

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22145 AN: 67930

Other (OTH) AF: 0.312 AC: 658 AN: 2108

Alfa AF: 0.273 Hom.: 1921

Bravo AF: 0.322

Asia WGS AF: 0.325 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.99
DANN	Benign	0.69
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs2010457; hg19: chr19-9958878; COSMIC: COSV56112804;