chr12-70560684-C-T

Variant names:

• chr12-70560684-C-T
• rs17108344
• NM_001109754.4:c.4419G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001109754.4(PTPRB):​c.4419G>A​(p.Ala1473Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00942 in 1,612,790 control chromosomes in the GnomAD database, including 524 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 0.033 (235 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (289 hom.)
• Consequence: PTPRB NM_001109754.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 8 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=-1.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRB	NM_001109754.4	MANE Select	c.4419G>A	p.Ala1473Ala	synonymous	Exon 17 of 34	NP_001103224.1
	PTPRB	NM_001330204.2		c.4155G>A	p.Ala1385Ala	synonymous	Exon 16 of 33	NP_001317133.1
	PTPRB	NM_002837.6		c.3765G>A	p.Ala1255Ala	synonymous	Exon 15 of 32	NP_002828.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRB	ENST00000334414.11	TSL:1 MANE Select	c.4419G>A	p.Ala1473Ala	synonymous	Exon 17 of 34	ENSP00000334928.6
	PTPRB	ENST00000261266.9	TSL:1	c.3765G>A	p.Ala1255Ala	synonymous	Exon 15 of 32	ENSP00000261266.5
	PTPRB	ENST00000538708.5	TSL:1	c.3495G>A	p.Ala1165Ala	synonymous	Exon 14 of 31	ENSP00000438927.1

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5052 AN: 151064 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.0194

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.0314

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.00294

Gnomad OTH AF: 0.0319

GnomAD2 exomes AF: 0.0139 AC: 3453 AN: 249034 AF XY: 0.0135

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00722

Gnomad ASJ exome AF: 0.0168

Gnomad EAS exome AF: 0.000223

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.00304

Gnomad OTH exome AF: 0.0132

GnomAD4 exome AF: 0.00694 AC: 10138 AN: 1461608 Hom.: 289 Cov.: 31 AF XY: 0.00737 AC XY: 5360 AN XY: 727094

African (AFR) AF: 0.109 AC: 3654 AN: 33478

American (AMR) AF: 0.00763 AC: 341 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0165 AC: 432 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.0296 AC: 2550 AN: 86238

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53398

Middle Eastern (MID) AF: 0.0384 AC: 220 AN: 5724

European-Non Finnish (NFE) AF: 0.00190 AC: 2116 AN: 1111850

Other (OTH) AF: 0.0135 AC: 812 AN: 60366

GnomAD4 genome AF: 0.0334 AC: 5054 AN: 151182 Hom.: 235 Cov.: 32 AF XY: 0.0326 AC XY: 2410 AN XY: 73890

African (AFR) AF: 0.106 AC: 4358 AN: 41116

American (AMR) AF: 0.0136 AC: 206 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.0194 AC: 67 AN: 3454

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5084

South Asian (SAS) AF: 0.0315 AC: 149 AN: 4736

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10584

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.00294 AC: 199 AN: 67732

Other (OTH) AF: 0.0315 AC: 66 AN: 2094

Alfa AF: 0.0128 Hom.: 133

Bravo AF: 0.0368

Asia WGS AF: 0.0140 AC: 49 AN: 3478

EpiCase AF: 0.00491

EpiControl AF: 0.00504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	4.4
DANN	Benign	0.50
PhyloP100		-1.8
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: rs17108344; hg19: chr12-70954464;