rs1975920

Variant names:

• chr12-27583053-G-T
• rs1975920
• NM_003622.4:c.-36+4814G>T

Variant summary

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

The ENST00000228425.11(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 ENST00000228425.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182
• Publications: 4 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000228425.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIBP1	NM_003622.4	MANE Select	c.-36+4814G>T		intron	N/A	NP_003613.4
	PPFIBP1	NM_177444.3		c.-36+4814G>T		intron	N/A	NP_803193.3
	PPFIBP1	NM_001198916.2		c.-36+4814G>T		intron	N/A	NP_001185845.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIBP1	ENST00000228425.11	TSL:1 MANE Select	c.-36+4814G>T		intron	N/A	ENSP00000228425.6
	PPFIBP1	ENST00000318304.12	TSL:1	c.-36+4814G>T		intron	N/A	ENSP00000314724.8
	PPFIBP1	ENST00000542629.5	TSL:1	c.-36+4814G>T		intron	N/A	ENSP00000443442.1

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

African (AFR) AF: 0.229 AC: 9476 AN: 41430

American (AMR) AF: 0.320 AC: 4890 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1786 AN: 3466

East Asian (EAS) AF: 0.127 AC: 659 AN: 5172

South Asian (SAS) AF: 0.408 AC: 1968 AN: 4822

European-Finnish (FIN) AF: 0.486 AC: 5121 AN: 10536

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34932 AN: 67950

Other (OTH) AF: 0.400 AC: 843 AN: 2108

Alfa AF: 0.722 Hom.: 15606

Bravo AF: 0.374

Asia WGS AF: 0.267 AC: 930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.7
DANN	Benign	0.56
PhyloP100		0.18
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: rs1975920; hg19: chr12-27735986; COSMIC: COSV99945752;