rs7121523

Positions:

• chr11-7578974-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001351860.2(PPFIBP2):​c.72G>A​(p.Thr24Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,860 control chromosomes in the GnomAD database, including 3,926 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3926 hom., cov: 31)
• Consequence: PPFIBP2 NM_001351860.2 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

Genes affected

PPFIBP2 (HGNC:9250): (PPFIA binding protein 2) This gene encodes a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. The encoded protein is a beta liprin and plays a role in axon guidance and neuronal synapse development by recruiting LAR protein-tyrosine phosphatases to the plasma membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

LOC105376535 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-3.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPFIBP2	NM_003621.5	c.279+13207G>A		intron_variant		ENST00000299492.9	NP_003612.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPFIBP2	ENST00000299492.9	c.279+13207G>A		intron_variant		1	NM_003621.5	ENSP00000299492.4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32682 AN: 151744 Hom.: 3911 Cov.: 31

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.216 AC: 32745 AN: 151860 Hom.: 3926 Cov.: 31 AF XY: 0.214 AC XY: 15849 AN XY: 74208

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.182

Alfa AF: 0.185 Hom.: 1730

Bravo AF: 0.227

Asia WGS AF: 0.241 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.087
DANN	Benign	0.55

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: rs7121523; hg19: chr11-7600205; COSMIC: COSV55079323;