chr11-7578974-G-A

Variant names:

• chr11-7578974-G-A
• rs7121523
• NM_003621.5:c.279+13207G>A

Variant summary

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

The NM_003621.5(PPFIBP2):​c.279+13207G>A variant causes a intron 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. 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_003621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• Publications: 4 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]

LOC105376535 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIBP2	NM_003621.5	MANE Select	c.279+13207G>A		intron	N/A	NP_003612.3
	PPFIBP2	NM_001351860.2		c.72G>A	p.Thr24Thr	splice_region synonymous	Exon 1 of 22	NP_001338789.2
	PPFIBP2	NM_001351853.2		c.279+13207G>A		intron	N/A	NP_001338782.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIBP2	ENST00000299492.9	TSL:1 MANE Select	c.279+13207G>A		intron	N/A	ENSP00000299492.4
	PPFIBP2	ENST00000533792.5	TSL:1	c.-196+2458G>A		intron	N/A	ENSP00000436498.1
	PPFIBP2	ENST00000684123.1		c.279+13207G>A		intron	N/A	ENSP00000507842.1

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

African (AFR) AF: 0.322 AC: 13330 AN: 41360

American (AMR) AF: 0.209 AC: 3193 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1352 AN: 5136

South Asian (SAS) AF: 0.212 AC: 1021 AN: 4810

European-Finnish (FIN) AF: 0.145 AC: 1529 AN: 10552

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11260 AN: 67960

Other (OTH) AF: 0.182 AC: 383 AN: 2102

Alfa AF: 0.185 Hom.: 2281

Bravo AF: 0.227

Asia WGS AF: 0.241 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.087
DANN	Benign	0.55
PhyloP100		-3.0
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: rs7121523; hg19: chr11-7600205; COSMIC: COSV55079323;