12-70832700-A-G

Variant names:

• chr12-70832700-A-G
• rs2470378
• NM_002849.4:c.357+59979T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002849.4(PTPRR):​c.357+59979T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,084 control chromosomes in the GnomAD database, including 12,546 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 0.35 (12546 hom., cov: 32)
• Consequence: PTPRR NM_002849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002849.4. 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
	PTPRR	NM_002849.4	MANE Select	c.357+59979T>C		intron	N/A	NP_002840.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRR	ENST00000283228.7	TSL:1 MANE Select	c.357+59979T>C		intron	N/A	ENSP00000283228.2

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52858 AN: 151968 Hom.: 12514 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.348 AC: 52956 AN: 152084 Hom.: 12546 Cov.: 32 AF XY: 0.341 AC XY: 25382 AN XY: 74348

African (AFR) AF: 0.680 AC: 28224 AN: 41476

American (AMR) AF: 0.316 AC: 4831 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3466

East Asian (EAS) AF: 0.173 AC: 893 AN: 5168

South Asian (SAS) AF: 0.159 AC: 765 AN: 4818

European-Finnish (FIN) AF: 0.186 AC: 1966 AN: 10584

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14605 AN: 67980

Other (OTH) AF: 0.328 AC: 693 AN: 2112

Alfa AF: 0.253 Hom.: 4028

Bravo AF: 0.375

Asia WGS AF: 0.214 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.77
PhyloP100		0.098
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: rs2470378; hg19: chr12-71226480;