11-7535346-A-G

Variant names:

• chr11-7535346-A-G
• rs12791447
• NM_003621.5:c.-36-14094A>G

Variant summary

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

The NM_003621.5(PPFIBP2):​c.-36-14094A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 152,290 control chromosomes in the GnomAD database, including 518 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 0.068 (518 hom., cov: 33)
• Consequence: PPFIBP2 NM_003621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 12 publications found

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]

LOC124902806 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003621.5. 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
	PPFIBP2	NM_003621.5	MANE Select	c.-36-14094A>G		intron	N/A	NP_003612.3	Q8ND30-1
	PPFIBP2	NM_001351853.2		c.-36-14094A>G		intron	N/A	NP_001338782.2
	PPFIBP2	NM_001351854.2		c.-36-14094A>G		intron	N/A	NP_001338783.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIBP2	ENST00000299492.9	TSL:1 MANE Select	c.-36-14094A>G		intron	N/A	ENSP00000299492.4	Q8ND30-1
	PPFIBP2	ENST00000684123.1		c.-36-14094A>G		intron	N/A	ENSP00000507842.1	A0A804HKA2
	PPFIBP2	ENST00000857461.1		c.-37+11568A>G		intron	N/A	ENSP00000527520.1

Frequencies

GnomAD3 genomes AF: 0.0684 AC: 10413 AN: 152172 Hom.: 512 Cov.: 33

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0829

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.0866

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

GnomAD4 genome AF: 0.0685 AC: 10427 AN: 152290 Hom.: 518 Cov.: 33 AF XY: 0.0721 AC XY: 5371 AN XY: 74474

African (AFR) AF: 0.0176 AC: 733 AN: 41578

American (AMR) AF: 0.164 AC: 2506 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3470

East Asian (EAS) AF: 0.116 AC: 602 AN: 5172

South Asian (SAS) AF: 0.136 AC: 659 AN: 4830

European-Finnish (FIN) AF: 0.0829 AC: 880 AN: 10614

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0661 AC: 4496 AN: 68022

Other (OTH) AF: 0.0848 AC: 179 AN: 2112

Alfa AF: 0.0722 Hom.: 964

Bravo AF: 0.0715

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.29
PhyloP100		-0.63
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: rs12791447; hg19: chr11-7556577;