Genetic Variant ENST00000591174.2:n.253C>T (chr19-9834895-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000591174.2(PIN1-DT):n.253C>T 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 0.0071 in 205,902 control chromosomes in the GnomAD database, including 29 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 0.0093 ( 28 hom., cov: 33)

Exomes 𝑓: 0.00073 ( 1 hom. )

Consequence

PIN1-DT
ENST00000591174.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.565

Publications

1 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=-0.79).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00933 (1422/152388) while in subpopulation AFR AF = 0.0329 (1370/41600). AF 95% confidence interval is 0.0315. There are 28 homozygotes in GnomAd4. There are 704 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIN1-DT	NR_183873.1 link	n.121C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
PIN1-DT	ENST00000591174.2 link	n.253C>T	non_coding_transcript_exon_variant	Exon 1 of 2	3
PIN1-DT	ENST00000731112.1 link	n.122C>T	non_coding_transcript_exon_variant	Exon 1 of 4
PIN1-DT	ENST00000731113.1 link	n.119C>T	non_coding_transcript_exon_variant	Exon 1 of 2
PIN1-DT	ENST00000731114.1 link	n.198C>T	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00931

AC:

1417

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00526

GnomAD4 exome

AF:

0.000729

AC:

AN:

53514

Hom.:

Cov.:

AF XY:

0.000743

AC XY:

AN XY:

28248

show subpopulations

African (AFR)

AF:

0.0335

AC:

AN:

1046

American (AMR)

AF:

0.00104

AC:

AN:

966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1444

East Asian (EAS)

AF:

0.00

AC:

AN:

1498

South Asian (SAS)

AF:

0.00

AC:

AN:

7842

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

204

European-Non Finnish (NFE)

AF:

0.0000291

AC:

AN:

34352

Other (OTH)

AF:

0.000612

AC:

AN:

3266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00933

AC:

1422

AN:

152388

Hom.:

Cov.:

AF XY:

0.00945

AC XY:

704

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.0329

AC:

1370

AN:

41600

American (AMR)

AF:

0.00235

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68042

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

142

212

283

354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00817

Hom.:

Bravo

AF:

0.0105

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.4

(source)

DANN

Benign

0.77

PhyloP100

0.56

PromoterAI

-0.026

Neutral

(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