Genetic Variant PIN1-DT:n.460C>G (chr19-9834503-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000591174.2(PIN1-DT):n.460C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,298 control chromosomes in the GnomAD database, including 2,147 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 0.15 ( 2144 hom., cov: 32)

Exomes 𝑓: 0.12 ( 3 hom. )

Consequence

PIN1-DT
ENST00000591174.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0560

Publications

52 publications found

Variant links:

Genes affected

PIN1-DT (HGNC:55303): (PIN1 divergent transcript)

PIN1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIN1-DT	NR_183873.1 link	n.328C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
PIN1-DT	ENST00000591174.2 link	n.460C>G	non_coding_transcript_exon_variant	Exon 2 of 2	3
PIN1-DT	ENST00000731113.1 link	n.415C>G	non_coding_transcript_exon_variant	Exon 2 of 2
PIN1-DT	ENST00000731114.1 link	n.423C>G	non_coding_transcript_exon_variant	Exon 2 of 2
PIN1-DT	ENST00000731112.1 link	n.311+18C>G	intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22385

AN:

151910

Hom.:

2144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.0332

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.0695

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.147

GnomAD4 exome

AF:

0.122

AC:

AN:

270

Hom.:

Cov.:

AF XY:

0.138

AC XY:

AN XY:

138

show subpopulations

African (AFR)

AF:

0.417

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0417

AC:

AN:

South Asian (SAS)

AF:

0.125

AC:

AN:

European-Finnish (FIN)

AF:

0.0500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.115

AC:

AN:

182

Other (OTH)

AF:

0.200

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.147

AC:

22402

AN:

152028

Hom.:

2144

Cov.:

AF XY:

0.146

AC XY:

10820

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.275

AC:

11381

AN:

41444

American (AMR)

AF:

0.100

AC:

1530

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

413

AN:

3470

East Asian (EAS)

AF:

0.0331

AC:

171

AN:

5172

South Asian (SAS)

AF:

0.155

AC:

746

AN:

4818

European-Finnish (FIN)

AF:

0.0695

AC:

734

AN:

10562

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6950

AN:

67998

Other (OTH)

AF:

0.146

AC:

309

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

922

1844

2765

3687

4609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0527

Hom.:

Bravo

AF:

0.151

Asia WGS

AF:

0.104

AC:

364

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.7

(source)

DANN

Benign

0.78

PhyloP100

0.056

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over