rs2278341

Variant names:

• chr12-70555840-G-A
• rs2278341
• NM_001109754.4:c.4993+30C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001109754.4(PTPRB):​c.4993+30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,603,946 control chromosomes in the GnomAD database, including 105,205 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 0.36 (9886 hom., cov: 32)
  • Exomes 𝑓: 0.36 (95319 hom.)
• Consequence: PTPRB NM_001109754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988
• Publications: 7 publications found

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]

ENSG00000299164 (HGNC:):

PTPRB-AS1 (HGNC:58150):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRB	NM_001109754.4	c.4993+30C>T		intron_variant	Intron 19 of 33	ENST00000334414.11	NP_001103224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRB	ENST00000334414.11	c.4993+30C>T		intron_variant	Intron 19 of 33	1	NM_001109754.4	ENSP00000334928.6

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54135 AN: 151866 Hom.: 9885 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.322

GnomAD2 exomes AF: 0.334 AC: 81156 AN: 242796 AF XY: 0.337

Gnomad AFR exome AF: 0.397

Gnomad AMR exome AF: 0.245

Gnomad ASJ exome AF: 0.300

Gnomad EAS exome AF: 0.206

Gnomad FIN exome AF: 0.419

Gnomad NFE exome AF: 0.354

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.359 AC: 521930 AN: 1451962 Hom.: 95319 Cov.: 35 AF XY: 0.359 AC XY: 258879 AN XY: 721266

African (AFR) AF: 0.396 AC: 13162 AN: 33220

American (AMR) AF: 0.246 AC: 10879 AN: 44142

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 7678 AN: 25914

East Asian (EAS) AF: 0.207 AC: 8168 AN: 39550

South Asian (SAS) AF: 0.360 AC: 30826 AN: 85536

European-Finnish (FIN) AF: 0.416 AC: 22102 AN: 53118

Middle Eastern (MID) AF: 0.279 AC: 1160 AN: 4152

European-Non Finnish (NFE) AF: 0.368 AC: 406730 AN: 1106446

Other (OTH) AF: 0.354 AC: 21225 AN: 59884

GnomAD4 genome AF: 0.356 AC: 54152 AN: 151984 Hom.: 9886 Cov.: 32 AF XY: 0.354 AC XY: 26330 AN XY: 74292

African (AFR) AF: 0.401 AC: 16619 AN: 41450

American (AMR) AF: 0.268 AC: 4096 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1032 AN: 3466

East Asian (EAS) AF: 0.193 AC: 993 AN: 5154

South Asian (SAS) AF: 0.345 AC: 1661 AN: 4814

European-Finnish (FIN) AF: 0.420 AC: 4429 AN: 10548

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24342 AN: 67962

Other (OTH) AF: 0.320 AC: 675 AN: 2108

Alfa AF: 0.342 Hom.: 12265

Bravo AF: 0.346

Asia WGS AF: 0.272 AC: 944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.77
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2278341; hg19: chr12-70949620; COSMIC: COSV54252746; COSMIC: COSV54252746;