12-15322057-TCA-TCACA

Variant names:

• chr12-15322057-T-TCA
• rs543534905
• ENST00000393736.3:c.-115+15319_-115+15320insTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000393736.3(RERG):​c.-115+15319_-115+15320insTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00758 in 152,206 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0076 (9 hom., cov: 32)
• Consequence: RERG ENST00000393736.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.152
• Publications: 0 publications found

Genes affected

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]

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]

PTPRO Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 6

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-15322057-T-TCA is Benign according to our data. Variant chr12-15322057-T-TCA is described in ClinVar as Likely_benign. ClinVar VariationId is 1707139.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00758 (1153/152206) while in subpopulation AFR AF = 0.0255 (1060/41512). AF 95% confidence interval is 0.0243. There are 9 homozygotes in GnomAd4. There are 558 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393736.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RERG	ENST00000393736.3	TSL:3	c.-115+15319_-115+15320insTG		intron	N/A	ENSP00000440887.1	F5GYR1
	PTPRO	ENST00000674316.1		c.-670_-669insCA		upstream_gene	N/A	ENSP00000501352.1	Q16827-1

Frequencies

GnomAD3 genomes AF: 0.00755 AC: 1149 AN: 152088 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00717

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

GnomAD4 genome AF: 0.00758 AC: 1153 AN: 152206 Hom.: 9 Cov.: 32 AF XY: 0.00750 AC XY: 558 AN XY: 74426

African (AFR) AF: 0.0255 AC: 1060 AN: 41512

American (AMR) AF: 0.00465 AC: 71 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68000

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00569 Hom.: 0

Bravo AF: 0.00891

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs543534905; hg19: chr12-15474991;