12-70550174-C-T

Variant names:

• chr12-70550174-C-T
• rs3782377
• NM_001109754.4:c.5387+2603G>A

Variant summary

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

The NM_001109754.4(PTPRB):​c.5387+2603G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,164 control chromosomes in the GnomAD database, including 2,949 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 (2949 hom., cov: 33)
• Consequence: PTPRB NM_001109754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 1 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]

PTPRB-AS1 (HGNC:58150):

ENSG00000299164 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRB	NM_001109754.4	c.5387+2603G>A		intron_variant	Intron 21 of 33	ENST00000334414.11	NP_001103224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRB	ENST00000334414.11	c.5387+2603G>A		intron_variant	Intron 21 of 33	1	NM_001109754.4	ENSP00000334928.6

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26998 AN: 152046 Hom.: 2948 Cov.: 33

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.177 AC: 26990 AN: 152164 Hom.: 2949 Cov.: 33 AF XY: 0.181 AC XY: 13467 AN XY: 74394

African (AFR) AF: 0.0466 AC: 1934 AN: 41544

American (AMR) AF: 0.254 AC: 3880 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 876 AN: 3466

East Asian (EAS) AF: 0.265 AC: 1368 AN: 5168

South Asian (SAS) AF: 0.178 AC: 856 AN: 4814

European-Finnish (FIN) AF: 0.225 AC: 2380 AN: 10600

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14927 AN: 67984

Other (OTH) AF: 0.202 AC: 425 AN: 2106

Alfa AF: 0.210 Hom.: 3968

Bravo AF: 0.175

Asia WGS AF: 0.203 AC: 706 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.2
DANN	Benign	0.55
PhyloP100		-0.021
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: rs3782377; hg19: chr12-70943954;