chr12-70856216-A-G

Variant names:

• chr12-70856216-A-G
• rs12229663
• NM_002849.4:c.357+36463T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002849.4(PTPRR):​c.357+36463T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,094 control chromosomes in the GnomAD database, including 4,120 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 0.23 (4120 hom., cov: 32)
• Consequence: PTPRR NM_002849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781

Genes affected

PTPRR (HGNC:9680): (protein tyrosine phosphatase receptor type R) 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 possesses an extracellular region, a single transmembrane region, and a single intracellular catalytic domain, and thus represents a receptor-type PTP. Silencing of this gene has been associated with colorectal cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares a symbol (PTPRQ) with another gene, protein tyrosine phosphatase, receptor type, Q (GeneID 374462), which is also located on chromosome 12. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRR	NM_002849.4	c.357+36463T>C		intron_variant	Intron 2 of 13	ENST00000283228.7	NP_002840.2
PTPRR	XM_011538615.3	c.333+36463T>C		intron_variant	Intron 2 of 13		XP_011536917.1
PTPRR	XM_047429233.1	c.357+36463T>C		intron_variant	Intron 2 of 11		XP_047285189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRR	ENST00000283228.7	c.357+36463T>C		intron_variant	Intron 2 of 13	1	NM_002849.4	ENSP00000283228.2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34246 AN: 151976 Hom.: 4119 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.225 AC: 34250 AN: 152094 Hom.: 4120 Cov.: 32 AF XY: 0.229 AC XY: 16994 AN XY: 74350

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.208

Alfa AF: 0.220 Hom.: 5967

Bravo AF: 0.215

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.64
DANN	Benign	0.71

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: rs12229663; hg19: chr12-71249996;