12-27536274-C-G

Position:

• chr12-27536274-C-G

Variant summary

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

The NM_003622.4(PPFIBP1):​c.-124+11909C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 152,334 control chromosomes in the GnomAD database, including 71,972 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 0.97 (71972 hom., cov: 32)
• Consequence: PPFIBP1 NM_003622.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPFIBP1	NM_003622.4	c.-124+11909C>G		intron_variant		ENST00000228425.11	NP_003613.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPFIBP1	ENST00000228425.11	c.-124+11909C>G		intron_variant		1	NM_003622.4	ENSP00000228425.6

Frequencies

GnomAD3 genomes AF: 0.972 AC: 147925 AN: 152216 Hom.: 71915 Cov.: 32

Gnomad AFR AF: 0.992

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.979

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

GnomAD4 genome AF: 0.972 AC: 148041 AN: 152334 Hom.: 71972 Cov.: 32 AF XY: 0.974 AC XY: 72556 AN XY: 74480

Gnomad4 AFR AF: 0.992

Gnomad4 AMR AF: 0.983

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.992

Gnomad4 FIN AF: 0.984

Gnomad4 NFE AF: 0.950

Gnomad4 OTH AF: 0.979

Alfa AF: 0.961 Hom.: 8729

Bravo AF: 0.972

Asia WGS AF: 0.997 AC: 3466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.37

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: rs708185; hg19: chr12-27689207;