XR_007063225.1:n.2063C>T

Variant names:

• chr12-15322293-G-A
• rs73057219
• XR_007063225.1:n.2063C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XR_007063225.1(LOC105369673):​n.2063C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 275,444 control chromosomes in the GnomAD database, including 9,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4239 hom., cov: 32)
  • Exomes 𝑓: 0.27 (4828 hom.)
• Consequence: LOC105369673 XR_007063225.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0780
• Publications: 4 publications found

Genes affected

LOC105369673 (HGNC:):

PTPRO (HGNC:9678): (protein tyrosine phosphatase receptor type O) This gene encodes a member of the R3 subtype family of receptor-type protein tyrosine phosphatases. These proteins are localized to the apical surface of polarized cells and may have tissue-specific functions through activation of Src family kinases. This gene contains two distinct promoters, and alternatively spliced transcript variants encoding multiple isoforms have been observed. The encoded proteins may have multiple isoform-specific and tissue-specific functions, including the regulation of osteoclast production and activity, inhibition of cell proliferation and facilitation of apoptosis. This gene is a candidate tumor suppressor, and decreased expression of this gene has been observed in several types of cancer. [provided by RefSeq, May 2011]

RERG (HGNC:15980): (RAS like estrogen regulated growth inhibitor) RERG, a member of the RAS superfamily of GTPases, inhibits cell proliferation and tumor formation (Finlin et al., 2001 [PubMed 11533059]).[supplied by OMIM, Mar 2009]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-15322293-G-A is Benign according to our data. Variant chr12-15322293-G-A is described in ClinVar as Benign. ClinVar VariationId is 1269902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRO	NM_030667.3	c.-434G>A		upstream_gene_variant		ENST00000281171.9	NP_109592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRO	ENST00000281171.9	c.-434G>A		upstream_gene_variant		1	NM_030667.3	ENSP00000281171.4

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33324 AN: 152024 Hom.: 4240 Cov.: 32

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.272 AC: 33580 AN: 123302 Hom.: 4828 AF XY: 0.267 AC XY: 17592 AN XY: 65888

African (AFR) AF: 0.117 AC: 105 AN: 898

American (AMR) AF: 0.169 AC: 662 AN: 3908

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 930 AN: 2852

East Asian (EAS) AF: 0.142 AC: 363 AN: 2550

South Asian (SAS) AF: 0.251 AC: 5996 AN: 23858

European-Finnish (FIN) AF: 0.258 AC: 1855 AN: 7202

Middle Eastern (MID) AF: 0.222 AC: 108 AN: 486

European-Non Finnish (NFE) AF: 0.291 AC: 21807 AN: 75062

Other (OTH) AF: 0.270 AC: 1754 AN: 6486

GnomAD4 genome AF: 0.219 AC: 33320 AN: 152142 Hom.: 4239 Cov.: 32 AF XY: 0.219 AC XY: 16256 AN XY: 74380

African (AFR) AF: 0.0968 AC: 4019 AN: 41518

American (AMR) AF: 0.197 AC: 3010 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3464

East Asian (EAS) AF: 0.123 AC: 636 AN: 5164

South Asian (SAS) AF: 0.238 AC: 1151 AN: 4826

European-Finnish (FIN) AF: 0.244 AC: 2580 AN: 10594

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20026 AN: 67966

Other (OTH) AF: 0.228 AC: 481 AN: 2114

Alfa AF: 0.247 Hom.: 644

Bravo AF: 0.209

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.51
PhyloP100		0.078
PromoterAI		0.025	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs73057219; hg19: chr12-15475227;