Variant chr15-64155818-A-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000942.5(PPIB):c.*204dupA variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 511,490 control chromosomes in the GnomAD database, including 391 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 189 hom., cov: 26)

Exomes 𝑓: 0.057 ( 202 hom. )

Consequence

PPIB
NM_000942.5 splice_region

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.514

Variant links:

Genes affected

PPIB (HGNC:9255): (peptidylprolyl isomerase B) The protein encoded by this gene is a cyclosporine-binding protein and is mainly located within the endoplasmic reticulum. It is associated with the secretory pathway and released in biological fluids. This protein can bind to cells derived from T- and B-lymphocytes, and may regulate cyclosporine A-mediated immunosuppression. Variants have been identified in this protein that give rise to recessive forms of osteogenesis imperfecta. [provided by RefSeq, Oct 2009]

PPIB links:

SNX22 (HGNC:16315): (sorting nexin 22) The protein encoded by this gene is a sorting nexin that is found in the cytoplasm, where it interacts with membrane-bound phosphatidylinositol 3-phosphate. The encoded protein may play a role in intracellular trafficking. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Dec 2012]

SNX22 links:

SNX22 (HGNC:):

SNX22 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 15-64155818-A-AT is Benign according to our data. Variant chr15-64155818-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 316695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
PPIB	NM_000942.5 linkuse as main transcript	c.*204dupA	splice_region_variant	5/5	ENST00000300026.4	NP_000933.1	P23284
PPIB	NM_000942.5 linkuse as main transcript	c.*204dupA	3_prime_UTR_variant	5/5	ENST00000300026.4	NP_000933.1	P23284
SNX22	NM_024798.3 linkuse as main transcript	c.*1312dupT	3_prime_UTR_variant	7/7	ENST00000325881.9	NP_079074.2	Q96L94-1A0A024R5Y5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PPIB	ENST00000300026.4 linkuse as main transcript	c.*204dupA	splice_region_variant	5/5	1	NM_000942.5	ENSP00000300026.4	P23284
PPIB	ENST00000300026 linkuse as main transcript	c.*204dupA	3_prime_UTR_variant	5/5	1	NM_000942.5	ENSP00000300026.4	P23284
SNX22	ENST00000325881.9 linkuse as main transcript	c.*1312dupT	3_prime_UTR_variant	7/7	1	NM_024798.3	ENSP00000323435.4	Q96L94-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

6601

AN:

65158

Hom.:

189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.0929

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.00337

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.0833

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.0984

GnomAD4 exome

AF:

0.0572

AC:

25537

AN:

446274

Hom.:

202

Cov.:

AF XY:

0.0591

AC XY:

13923

AN XY:

235716

show subpopulations

Gnomad4 AFR exome

AF:

0.00879

Gnomad4 AMR exome

AF:

0.0256

Gnomad4 ASJ exome

AF:

0.0951

Gnomad4 EAS exome

AF:

0.000129

Gnomad4 SAS exome

AF:

0.0809

Gnomad4 FIN exome

AF:

0.0675

Gnomad4 NFE exome

AF:

0.0595

Gnomad4 OTH exome

AF:

0.0541

GnomAD4 genome

AF:

0.101

AC:

6593

AN:

65216

Hom.:

189

Cov.:

AF XY:

0.103

AC XY:

3244

AN XY:

31498

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.0929

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.00336

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.329

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.0986

Alfa

AF:

0.0452

Hom.:

Asia WGS

AF:

0.0280

AC:

AN:

3440

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Osteogenesis Imperfecta, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over