rs552282

Positions:

• chr11-70383065-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003626.5(PPFIA1):​c.*75G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 409,048 control chromosomes in the GnomAD database, including 31,813 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 0.43 (16041 hom., cov: 33)
  • Exomes 𝑓: 0.34 (15772 hom.)
• Consequence: PPFIA1 NM_003626.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390

Genes affected

PPFIA1 (HGNC:9245): (PTPRF interacting protein alpha 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. This protein binds to the intracellular membrane-distal phosphatase domain of tyrosine phosphatase LAR, and appears to localize LAR to cell focal adhesions. This interaction may regulate the disassembly of focal adhesion and thus help orchestrate cell-matrix interactions. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

CTTN-DT (HGNC:55592): (CTTN divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPFIA1	NM_003626.5	c.*75G>A		3_prime_UTR_variant	28/28	ENST00000253925.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPFIA1	ENST00000253925.12	c.*75G>A		3_prime_UTR_variant	28/28	1	NM_003626.5	P1
CTTN-DT	ENST00000530690.1	n.266-10531C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65920 AN: 151828 Hom.: 16016 Cov.: 33

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.419

GnomAD3 exomes AF: 0.335 AC: 30305 AN: 90372 Hom.: 5500 AF XY: 0.331 AC XY: 16736 AN XY: 50536

Gnomad AFR exome AF: 0.634

Gnomad AMR exome AF: 0.419

Gnomad ASJ exome AF: 0.291

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.326

Gnomad FIN exome AF: 0.403

Gnomad NFE exome AF: 0.327

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.341 AC: 87654 AN: 257102 Hom.: 15772 Cov.: 0 AF XY: 0.338 AC XY: 50500 AN XY: 149396

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.295

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.335

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.434 AC: 65999 AN: 151946 Hom.: 16041 Cov.: 33 AF XY: 0.433 AC XY: 32181 AN XY: 74266

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.419

Alfa AF: 0.367 Hom.: 11446

Bravo AF: 0.443

Asia WGS AF: 0.273 AC: 952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs552282; hg19: chr11-70229171;