chr11-70302968-G-A

Position:

• chr11-70302968-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.265-21434G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,908 control chromosomes in the GnomAD database, including 3,526 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 0.21 (3526 hom., cov: 31)
• Consequence: PPFIA1 NM_003626.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPFIA1	NM_003626.5	c.265-21434G>A		intron_variant		ENST00000253925.12
LOC107984346	XR_001748288.2	n.101-1803C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPFIA1	ENST00000253925.12	c.265-21434G>A		intron_variant		1	NM_003626.5	P1
	ENST00000528607.1	n.494-20556C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31705 AN: 151790 Hom.: 3528 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0876

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.209 AC: 31722 AN: 151908 Hom.: 3526 Cov.: 31 AF XY: 0.211 AC XY: 15675 AN XY: 74224

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.0876

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.238

Alfa AF: 0.221 Hom.: 1792

Bravo AF: 0.197

Asia WGS AF: 0.191 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.79

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: rs624765; hg19: chr11-70149074;