chr12-70555053-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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 -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109754.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRB	NM_001109754.4	MANE Select	c.5143+107T>C		intron	N/A	NP_001103224.1	P23467-3
	PTPRB	NM_001330204.2		c.4879+107T>C		intron	N/A	NP_001317133.1	F8VU56
	PTPRB	NM_002837.6		c.4489+107T>C		intron	N/A	NP_002828.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRB	ENST00000334414.11	TSL:1 MANE Select	c.5143+107T>C		intron	N/A	ENSP00000334928.6	P23467-3
	PTPRB	ENST00000261266.9	TSL:1	c.4489+107T>C		intron	N/A	ENSP00000261266.5	P23467-1
	PTPRB	ENST00000538708.5	TSL:1	c.4219+107T>C		intron	N/A	ENSP00000438927.1	P23467-4

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

African (AFR) AF: 0.000308 AC: 8 AN: 25950

American (AMR) AF: 0.00104 AC: 28 AN: 26804

Ashkenazi Jewish (ASJ) AF: 0.00196 AC: 37 AN: 18876

East Asian (EAS) AF: 0.00 AC: 0 AN: 36412

South Asian (SAS) AF: 0.000124 AC: 8 AN: 64554

European-Finnish (FIN) AF: 0.000600 AC: 29 AN: 48334

Middle Eastern (MID) AF: 0.00120 AC: 5 AN: 4174

European-Non Finnish (NFE) AF: 0.00143 AC: 1285 AN: 898996

Other (OTH) AF: 0.00118 AC: 59 AN: 49896

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

African (AFR) AF: 0.000241 AC: 10 AN: 41544

American (AMR) AF: 0.00157 AC: 24 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000472 AC: 5 AN: 10590

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00176 AC: 120 AN: 68002

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.0000479 Hom.: 3073

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.7
DANN	Benign	0.89
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism

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;