12-70555053-A-G

Position:

• chr12-70555053-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001109754.4(PTPRB):​c.5143+107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,326,202 control chromosomes in the GnomAD database, including 2 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 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: PTPRB NM_001109754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BS2: High AC in GnomAd4 at 169 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRB	NM_001109754.4	c.5143+107T>C		intron_variant		ENST00000334414.11	NP_001103224.1
LOC105369828	XR_001749196.2	n.10007-2927A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRB	ENST00000334414.11	c.5143+107T>C		intron_variant		1	NM_001109754.4	ENSP00000334928	A1

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 169 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00176

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.00124 AC: 1459 AN: 1173996 Hom.: 2 AF XY: 0.00126 AC XY: 737 AN XY: 583594

Gnomad4 AFR exome AF: 0.000308

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.00196

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000124

Gnomad4 FIN exome AF: 0.000600

Gnomad4 NFE exome AF: 0.00143

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.00111 AC: 169 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74404

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.00176

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.0000697 Hom.: 1893

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.7
DANN	Benign	0.89

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: rs2278342; hg19: chr12-70948833;