12-70554290-T-C

Position:

• chr12-70554290-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.5143+870A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,176 control chromosomes in the GnomAD database, including 52,795 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 0.82 (52795 hom., cov: 32)
• Consequence: PTPRB NM_001109754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRB	NM_001109754.4	c.5143+870A>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.5143+870A>G		intron_variant		1	NM_001109754.4	ENSP00000334928.6

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124456 AN: 152058 Hom.: 52765 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.818 AC: 124534 AN: 152176 Hom.: 52795 Cov.: 32 AF XY: 0.824 AC XY: 61297 AN XY: 74402

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.967

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.831

Alfa AF: 0.896 Hom.: 88090

Bravo AF: 0.793

Asia WGS AF: 0.929 AC: 3231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.7
DANN	Benign	0.87

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: rs2567133; hg19: chr12-70948070;