Genetic Variant PPFIBP2:c.888+63C>G (chr11-7628409-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003621.5(PPFIBP2):c.888+63C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,457,538 control chromosomes in the GnomAD database, including 158,911 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 0.51 ( 20732 hom., cov: 32)

Exomes 𝑓: 0.46 ( 138179 hom. )

Consequence

PPFIBP2
NM_003621.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.352

Publications

8 publications found

Variant links:

Genes affected

PPFIBP2 (HGNC:9250): (PPFIA binding protein 2) This gene encodes a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. The encoded protein is a beta liprin and plays a role in axon guidance and neuronal synapse development by recruiting LAR protein-tyrosine phosphatases to the plasma membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

PPFIBP2 links:

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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=-0.67).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003621.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPFIBP2	NM_003621.5	MANE Select	c.888+63C>G	intron	N/A	NP_003612.3	Q8ND30-1
PPFIBP2	NM_001351853.2		c.888+63C>G	intron	N/A	NP_001338782.2
PPFIBP2	NM_001351854.2		c.888+63C>G	intron	N/A	NP_001338783.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPFIBP2	ENST00000299492.9	TSL:1 MANE Select	c.888+63C>G	intron	N/A	ENSP00000299492.4	Q8ND30-1
PPFIBP2	ENST00000533792.5	TSL:1	c.414+63C>G	intron	N/A	ENSP00000436498.1	E9PP16
PPFIBP2	ENST00000684123.1		c.888+63C>G	intron	N/A	ENSP00000507842.1	A0A804HKA2

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77780

AN:

151898

Hom.:

20712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.549

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.517

GnomAD4 exome

AF:

0.457

AC:

596937

AN:

1305522

Hom.:

138179

AF XY:

0.454

AC XY:

298368

AN XY:

657188

show subpopulations

African (AFR)

AF:

0.686

AC:

20695

AN:

30164

American (AMR)

AF:

0.386

AC:

16588

AN:

43020

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

12041

AN:

24784

East Asian (EAS)

AF:

0.631

AC:

24477

AN:

38798

South Asian (SAS)

AF:

0.357

AC:

28982

AN:

81072

European-Finnish (FIN)

AF:

0.416

AC:

22086

AN:

53066

Middle Eastern (MID)

AF:

0.510

AC:

2781

AN:

5450

European-Non Finnish (NFE)

AF:

0.455

AC:

443235

AN:

973936

Other (OTH)

AF:

0.472

AC:

26052

AN:

55232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

15547

31094

46640

62187

77734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12726

25452

38178

50904

63630

<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:

0.512

AC:

77841

AN:

152016

Hom.:

20732

Cov.:

AF XY:

0.507

AC XY:

37649

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.670

AC:

27740

AN:

41426

American (AMR)

AF:

0.441

AC:

6735

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

1668

AN:

3470

East Asian (EAS)

AF:

0.619

AC:

3194

AN:

5162

South Asian (SAS)

AF:

0.348

AC:

1678

AN:

4824

European-Finnish (FIN)

AF:

0.411

AC:

4347

AN:

10572

Middle Eastern (MID)

AF:

0.497

AC:

145

AN:

292

European-Non Finnish (NFE)

AF:

0.452

AC:

30749

AN:

67964

Other (OTH)

AF:

0.514

AC:

1084

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1896

3792

5688

7584

9480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.307

Hom.:

687

Bravo

AF:

0.527

Asia WGS

AF:

0.461

AC:

1603

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over