chr12-15322293-G-A

Position:

• chr12-15322293-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XR_007063224.1(LOC105369673):​n.332+15084C>T variant causes a intron, non coding transcript 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_007063224.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0780

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

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
LOC105369673	XR_007063224.1	n.332+15084C>T		intron_variant, non_coding_transcript_variant
LOC105369673	XR_007063225.1	n.2063C>T		non_coding_transcript_exon_variant	3/3
LOC105369673	XR_007063226.1	n.2092C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRO	ENST00000674316.1	c.-434G>A		5_prime_UTR_variant	1/26			ENSP00000501352	P4
RERG	ENST00000393736.3	c.-115+15084C>T		intron_variant		3		ENSP00000440887

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

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.326

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.270

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

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.228

Alfa AF: 0.253 Hom.: 640

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73057219; hg19: chr12-15475227;