rs2278342

chr12-70555053-A-Cchr12-70555053-A-Gchr12-70555053-A-T

Variant summary

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

The NM_001109754.4(PTPRB):c.5143+107T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,324,302 control chromosomes in the GnomAD database, including 42,358 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 (4364 hom., cov: 32)
  • Exomes 𝑓: 0.24 (37994 hom.)
• Consequence: PTPRB NM_001109754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRB	NM_001109754.4	c.5143+107T>G		intron_variant		ENST00000334414.11
LOC105369828	XR_001749196.2	n.10007-2927A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRB	ENST00000334414.11	c.5143+107T>G		intron_variant		1	NM_001109754.4	A1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31789 AN: 152050 Hom.: 4357 Cov.: 32

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.241 AC: 282134 AN: 1172134 Hom.: 37994 AF XY: 0.243 AC XY: 141859 AN XY: 582650

Gnomad4 AFR exome AF: 0.0598

Gnomad4 AMR exome AF: 0.306

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.604

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.209 AC: 31820 AN: 152168 Hom.: 4364 Cov.: 32 AF XY: 0.217 AC XY: 16115 AN XY: 74382

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.244

Alfa AF: 0.212 Hom.: 1893

Bravo AF: 0.204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	5.6
Dann	Benign	0.88

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: rs2278342; hg19: chr12-70948833; COSMIC: COSV54254792; COSMIC: COSV54254792;