11-70344214-G-A

Position:

• chr11-70344214-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.1931+322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,170 control chromosomes in the GnomAD database, including 2,694 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 0.18 (2694 hom., cov: 32)
• Consequence: PPFIA1 NM_003626.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPFIA1	NM_003626.5	c.1931+322G>A		intron_variant		ENST00000253925.12	NP_003617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPFIA1	ENST00000253925.12	c.1931+322G>A		intron_variant		1	NM_003626.5	ENSP00000253925	P1
	ENST00000528607.1	n.493+18662C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26656 AN: 152052 Hom.: 2696 Cov.: 32

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0889

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.175 AC: 26664 AN: 152170 Hom.: 2694 Cov.: 32 AF XY: 0.180 AC XY: 13368 AN XY: 74380

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.0889

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.204

Alfa AF: 0.198 Hom.: 3147

Bravo AF: 0.163

Asia WGS AF: 0.184 AC: 639 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	0.90
DANN	Benign	0.44

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: rs3781646; hg19: chr11-70190320;