rs2567137

Positions:

• chr12-70550470-G-A
• chr12-70550470-G-C

Variant summary

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

The NM_001109754.4(PTPRB):​c.5387+2307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,958 control chromosomes in the GnomAD database, including 9,883 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 0.35 (9883 hom., cov: 31)
• Consequence: PTPRB NM_001109754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

Genes affected

PTPRB (HGNC:9665): (protein tyrosine phosphatase receptor type B) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an extracellular domain, a single transmembrane segment and one intracytoplasmic catalytic domain, thus belongs to receptor type PTP. The extracellular region of this PTP is composed of multiple fibronectin type_III repeats, which was shown to interact with neuronal receptor and cell adhesion molecules, such as contactin and tenascin C. This protein was also found to interact with sodium channels, and thus may regulate sodium channels by altering tyrosine phosphorylation status. The functions of the interaction partners of this protein implicate the roles of this PTP in cell adhesion, neurite growth, and neuronal differentiation. Alternate transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

LOC105369828 (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 = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRB	NM_001109754.4	c.5387+2307C>T		intron_variant		ENST00000334414.11	NP_001103224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRB	ENST00000334414.11	c.5387+2307C>T		intron_variant		1	NM_001109754.4	ENSP00000334928.6

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52868 AN: 151840 Hom.: 9874 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.348 AC: 52901 AN: 151958 Hom.: 9883 Cov.: 31 AF XY: 0.359 AC XY: 26638 AN XY: 74270

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.352

Alfa AF: 0.373 Hom.: 14406

Bravo AF: 0.337

Asia WGS AF: 0.515 AC: 1793 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	0.52
DANN	Benign	0.35

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: rs2567137; hg19: chr12-70944250;