NM_001109754.4:c.708+231A>G

Variant names:

• chr12-70622159-T-C
• rs10506598
• NM_001109754.4:c.708+231A>G

Variant summary

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

The NM_001109754.4(PTPRB):​c.708+231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,066 control chromosomes in the GnomAD database, including 6,303 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 0.28 (6303 hom., cov: 32)
• Consequence: PTPRB NM_001109754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRB	NM_001109754.4	c.708+231A>G		intron_variant	Intron 3 of 33	ENST00000334414.11	NP_001103224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRB	ENST00000334414.11	c.708+231A>G		intron_variant	Intron 3 of 33	1	NM_001109754.4	ENSP00000334928.6

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42971 AN: 151948 Hom.: 6288 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.283 AC: 43043 AN: 152066 Hom.: 6303 Cov.: 32 AF XY: 0.286 AC XY: 21245 AN XY: 74356

African (AFR) AF: 0.340 AC: 14105 AN: 41488

American (AMR) AF: 0.318 AC: 4865 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3464

East Asian (EAS) AF: 0.217 AC: 1119 AN: 5150

South Asian (SAS) AF: 0.297 AC: 1430 AN: 4822

European-Finnish (FIN) AF: 0.291 AC: 3081 AN: 10580

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16768 AN: 67962

Other (OTH) AF: 0.289 AC: 609 AN: 2110

Alfa AF: 0.262 Hom.: 10326

Bravo AF: 0.287

Asia WGS AF: 0.264 AC: 916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		0.17
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: rs10506598; hg19: chr12-71015939;