rs2278342

Variant names:

• chr12-70555053-A-C
• rs2278342
• NM_001109754.4:c.5143+107T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-70555053-A-C
• chr12-70555053-A-G
• chr12-70555053-A-T

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+107T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,324,302 control chromosomes in the GnomAD database, including 42,358 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 0.21 (4364 hom., cov: 32)
  • Exomes 𝑓: 0.24 (37994 hom.)
• Consequence: PTPRB NM_001109754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• Publications: 4 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRB	NM_001109754.4	c.5143+107T>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+107T>G		intron_variant	Intron 20 of 33	1	NM_001109754.4	ENSP00000334928.6

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31789 AN: 152050 Hom.: 4357 Cov.: 32

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.241 AC: 282134 AN: 1172134 Hom.: 37994 AF XY: 0.243 AC XY: 141859 AN XY: 582650

African (AFR) AF: 0.0598 AC: 1550 AN: 25930

American (AMR) AF: 0.306 AC: 8189 AN: 26744

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 7103 AN: 18860

East Asian (EAS) AF: 0.604 AC: 21961 AN: 36352

South Asian (SAS) AF: 0.328 AC: 21101 AN: 64410

European-Finnish (FIN) AF: 0.249 AC: 12012 AN: 48290

Middle Eastern (MID) AF: 0.268 AC: 1117 AN: 4162

European-Non Finnish (NFE) AF: 0.219 AC: 196655 AN: 897560

Other (OTH) AF: 0.250 AC: 12446 AN: 49826

GnomAD4 genome AF: 0.209 AC: 31820 AN: 152168 Hom.: 4364 Cov.: 32 AF XY: 0.217 AC XY: 16115 AN XY: 74382

African (AFR) AF: 0.0639 AC: 2656 AN: 41538

American (AMR) AF: 0.276 AC: 4216 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3468

East Asian (EAS) AF: 0.604 AC: 3117 AN: 5158

South Asian (SAS) AF: 0.339 AC: 1632 AN: 4820

European-Finnish (FIN) AF: 0.260 AC: 2747 AN: 10584

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15340 AN: 67996

Other (OTH) AF: 0.244 AC: 515 AN: 2114

Alfa AF: 0.222 Hom.: 3073

Bravo AF: 0.204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.6
DANN	Benign	0.88
PhyloP100		-0.26
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: rs2278342; hg19: chr12-70948833; COSMIC: COSV54254792; COSMIC: COSV54254792;