19-9836241-A-G

Variant names:

• chr19-9836241-A-G
• rs1077220
• NM_006221.4:c.58+839A>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.58+839A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,548 control chromosomes in the GnomAD database, including 42,398 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 0.74 (42262 hom., cov: 32)
  • Exomes 𝑓: 0.76 (136 hom.)
• Consequence: PIN1 NM_006221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 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.58+839A>G		intron	N/A	NP_006212.1
	PIN1	NR_038422.3		n.86-582A>G		intron	N/A
	PIN1	NR_038830.2		n.86-582A>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.58+839A>G		intron	N/A	ENSP00000247970.5
	PIN1	ENST00000380889.6	TSL:1	n.571-114A>G		intron	N/A
	PIN1	ENST00000586025.5	TSL:2	n.911A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112745 AN: 151982 Hom.: 42250 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.755

GnomAD4 exome AF: 0.757 AC: 339 AN: 448 Hom.: 136 Cov.: 0 AF XY: 0.763 AC XY: 206 AN XY: 270

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AF: 0.676 AC: 46 AN: 68

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 3 AN: 4

East Asian (EAS) AF: 0.300 AC: 3 AN: 10

South Asian (SAS) AF: 0.722 AC: 26 AN: 36

European-Finnish (FIN) AF: 1.00 AC: 6 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.804 AC: 238 AN: 296

Other (OTH) AF: 0.636 AC: 14 AN: 22

GnomAD4 genome AF: 0.742 AC: 112809 AN: 152100 Hom.: 42262 Cov.: 32 AF XY: 0.737 AC XY: 54793 AN XY: 74344

African (AFR) AF: 0.748 AC: 31014 AN: 41484

American (AMR) AF: 0.763 AC: 11661 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2793 AN: 3472

East Asian (EAS) AF: 0.427 AC: 2204 AN: 5164

South Asian (SAS) AF: 0.603 AC: 2911 AN: 4824

European-Finnish (FIN) AF: 0.702 AC: 7418 AN: 10568

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52420 AN: 67984

Other (OTH) AF: 0.749 AC: 1581 AN: 2110

Alfa AF: 0.769 Hom.: 58192

Bravo AF: 0.745

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		0.052
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: rs1077220; hg19: chr19-9946917;