12-27536274-C-G

Variant names:

• chr12-27536274-C-G
• rs708185
• NM_003622.4:c.-124+11909C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003622.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIBP1	NM_003622.4	MANE Select	c.-124+11909C>G		intron	N/A	NP_003613.4
	PPFIBP1	NM_177444.3		c.-124+11909C>G		intron	N/A	NP_803193.3	Q86W92-1
	PPFIBP1	NM_001198916.2		c.-124+11909C>G		intron	N/A	NP_001185845.2	Q86W92-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIBP1	ENST00000228425.11	TSL:1 MANE Select	c.-124+11909C>G		intron	N/A	ENSP00000228425.6	Q86W92-2
	PPFIBP1	ENST00000318304.12	TSL:1	c.-124+11909C>G		intron	N/A	ENSP00000314724.8	Q86W92-1
	PPFIBP1	ENST00000542629.5	TSL:1	c.-124+11909C>G		intron	N/A	ENSP00000443442.1	Q86W92-4

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

African (AFR) AF: 0.992 AC: 41241 AN: 41576

American (AMR) AF: 0.983 AC: 15045 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3432 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5189 AN: 5190

South Asian (SAS) AF: 0.992 AC: 4790 AN: 4828

European-Finnish (FIN) AF: 0.984 AC: 10453 AN: 10618

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64633 AN: 68034

Other (OTH) AF: 0.979 AC: 2066 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.37
PhyloP100		-0.25
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: rs708185; hg19: chr12-27689207;