rs2287838

Variant names:

• chr19-9848338-G-A
• rs2287838
• NM_006221.4:c.382+198G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-9848338-G-A
• chr19-9848338-G-C
• chr19-9848338-G-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.382+198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 592,752 control chromosomes in the GnomAD database, including 70,989 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 0.41 (15450 hom., cov: 33)
  • Exomes 𝑓: 0.49 (55539 hom.)
• Consequence: PIN1 NM_006221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIN1	NM_006221.4	c.382+198G>A		intron_variant	Intron 3 of 3	ENST00000247970.9	NP_006212.1
PIN1	NR_038422.3	n.462+198G>A		intron_variant	Intron 4 of 4
PIN1	NR_038830.2	n.462+198G>A		intron_variant	Intron 4 of 5
PIN1	XM_011528068.3	c.397+198G>A		intron_variant	Intron 5 of 5		XP_011526370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIN1	ENST00000247970.9	c.382+198G>A		intron_variant	Intron 3 of 3	1	NM_006221.4	ENSP00000247970.5

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61866 AN: 151942 Hom.: 15454 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 0.488 AC: 214873 AN: 440694 Hom.: 55539 Cov.: 2 AF XY: 0.478 AC XY: 111584 AN XY: 233478

African (AFR) AF: 0.117 AC: 1448 AN: 12338

American (AMR) AF: 0.584 AC: 11329 AN: 19414

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 6999 AN: 13346

East Asian (EAS) AF: 0.313 AC: 9412 AN: 30100

South Asian (SAS) AF: 0.299 AC: 13807 AN: 46206

European-Finnish (FIN) AF: 0.565 AC: 15914 AN: 28156

Middle Eastern (MID) AF: 0.407 AC: 769 AN: 1890

European-Non Finnish (NFE) AF: 0.543 AC: 143207 AN: 263886

Other (OTH) AF: 0.473 AC: 11988 AN: 25358

GnomAD4 genome AF: 0.407 AC: 61861 AN: 152058 Hom.: 15450 Cov.: 33 AF XY: 0.406 AC XY: 30179 AN XY: 74322

African (AFR) AF: 0.114 AC: 4733 AN: 41520

American (AMR) AF: 0.545 AC: 8326 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1853 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1543 AN: 5158

South Asian (SAS) AF: 0.306 AC: 1473 AN: 4818

European-Finnish (FIN) AF: 0.535 AC: 5660 AN: 10584

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36964 AN: 67922

Other (OTH) AF: 0.421 AC: 891 AN: 2114

Alfa AF: 0.481 Hom.: 2463

Bravo AF: 0.397

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.32
PhyloP100		-0.84
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: rs2287838; hg19: chr19-9959014;