chr12-27573437-G-A

Variant names:

• chr12-27573437-G-A
• rs10506025
• NM_003622.4:c.-123-4715G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003622.4(PPFIBP1):​c.-123-4715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,956 control chromosomes in the GnomAD database, including 7,861 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 0.31 (7861 hom., cov: 31)
• Consequence: PPFIBP1 NM_003622.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 3 publications found

Genes affected

PPFIBP1 (HGNC:9249): (PPFIA binding protein 1) The protein encoded by this gene is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. Liprins interact with members of LAR family of transmembrane protein tyrosine phosphatases, which are known to be important for axon guidance and mammary gland development. It has been proposed that liprins are multivalent proteins that form complex structures and act as scaffolds for the recruitment and anchoring of LAR family of tyrosine phosphatases. This protein was found to interact with S100A4, a calcium-binding protein related to tumor invasiveness and metastasis. In vitro experiment demonstrated that the interaction inhibited the phosphorylation of this protein by protein kinase C and protein kinase CK2. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

PPFIBP1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: STRONG Submitted by: G2P
• neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities

  Inheritance: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIBP1	NM_003622.4	c.-123-4715G>A		intron_variant	Intron 1 of 29	ENST00000228425.11	NP_003613.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIBP1	ENST00000228425.11	c.-123-4715G>A		intron_variant	Intron 1 of 29	1	NM_003622.4	ENSP00000228425.6

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47380 AN: 151838 Hom.: 7855 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.373

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47407 AN: 151956 Hom.: 7861 Cov.: 31 AF XY: 0.311 AC XY: 23101 AN XY: 74280

African (AFR) AF: 0.206 AC: 8558 AN: 41452

American (AMR) AF: 0.321 AC: 4896 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3466

East Asian (EAS) AF: 0.281 AC: 1442 AN: 5140

South Asian (SAS) AF: 0.295 AC: 1421 AN: 4814

European-Finnish (FIN) AF: 0.304 AC: 3214 AN: 10558

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.368 AC: 25029 AN: 67940

Other (OTH) AF: 0.376 AC: 794 AN: 2112

Alfa AF: 0.354 Hom.: 41264

Bravo AF: 0.310

Asia WGS AF: 0.277 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.49
PhyloP100		0.21
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: rs10506025; hg19: chr12-27726370;