rs1975920

chr12-27583053-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003622.4(PPFIBP1):c.-36+4814G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,982 control chromosomes in the GnomAD database, including 13,330 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 0.40 (13330 hom., cov: 32)
• Consequence: PPFIBP1 NM_003622.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPFIBP1	NM_003622.4	c.-36+4814G>T		intron_variant		ENST00000228425.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPFIBP1	ENST00000228425.11	c.-36+4814G>T		intron_variant		1	NM_003622.4	P3

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60168 AN: 151864 Hom.: 13324 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.396 AC: 60190 AN: 151982 Hom.: 13330 Cov.: 32 AF XY: 0.392 AC XY: 29138 AN XY: 74290

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.400

Alfa AF: 0.681 Hom.: 11717

Bravo AF: 0.374

Asia WGS AF: 0.267 AC: 930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	2.7
Dann	Benign	0.56

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

Other links and lift over

dbSNP: rs1975920; hg19: chr12-27735986; COSMIC: COSV99945752;