12-70554290-T-C

Variant names:

• chr12-70554290-T-C
• rs2567133
• NM_001109754.4:c.5143+870A>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.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
• Publications: 2 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=-0.82).
• 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 rank	MANE	Protein	UniProt
PTPRB	NM_001109754.4	c.5143+870A>G		intron_variant	Intron 20 of 33	ENST00000334414.11	NP_001103224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRB	ENST00000334414.11	c.5143+870A>G		intron_variant	Intron 20 of 33	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

African (AFR) AF: 0.573 AC: 23767 AN: 41446

American (AMR) AF: 0.814 AC: 12446 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3141 AN: 3472

East Asian (EAS) AF: 0.967 AC: 5011 AN: 5182

South Asian (SAS) AF: 0.943 AC: 4552 AN: 4826

European-Finnish (FIN) AF: 0.967 AC: 10262 AN: 10616

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.920 AC: 62586 AN: 68024

Other (OTH) AF: 0.831 AC: 1758 AN: 2116

Alfa AF: 0.886 Hom.: 129486

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
PhyloP100		0.35
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: rs2567133; hg19: chr12-70948070;