chr12-70622159-T-C

Position:

• chr12-70622159-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PTPRB	NM_001109754.4	c.708+231A>G		intron_variant		ENST00000334414.11	NP_001103224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRB	ENST00000334414.11	c.708+231A>G		intron_variant		1	NM_001109754.4	ENSP00000334928	A1

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

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.289

Alfa AF: 0.258 Hom.: 7377

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

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: rs10506598; hg19: chr12-71015939;