Variant 12-15121064-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_032918.3(RERG):c.117C>T(p.Leu39=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,610,246 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 19 hom. )

Consequence

RERG
NM_032918.3 splice_region, synonymous

Scores

Splicing: ADA: 0.009486

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.967

Variant links:

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]

RERG links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 12-15121064-G-A is Benign according to our data. Variant chr12-15121064-G-A is described in ClinVar as [Benign]. Clinvar id is 781697.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.967 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RERG	NM_032918.3 linkuse as main transcript	c.117C>T	p.Leu39=	splice_region_variant, synonymous_variant	3/5	ENST00000256953.6	NP_116307.1
RERG	XM_047429797.1 linkuse as main transcript	c.108C>T	p.Leu36=	splice_region_variant, synonymous_variant	3/5		XP_047285753.1
RERG	XM_047429798.1 linkuse as main transcript	c.117C>T	p.Leu39=	splice_region_variant, synonymous_variant	3/6		XP_047285754.1
RERG	NM_001190726.2 linkuse as main transcript	c.62-9647C>T		intron_variant			NP_001177655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RERG	ENST00000256953.6 linkuse as main transcript	c.117C>T	p.Leu39=	splice_region_variant, synonymous_variant	3/5	1	NM_032918.3	ENSP00000256953	P1	Q96A58-1

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

188

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.0331

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00190

AC:

476

AN:

250380

Hom.:

AF XY:

0.00194

AC XY:

263

AN XY:

135306

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.0367

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000787

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00138

AC:

2018

AN:

1458032

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

971

AN XY:

725510

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0340

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000858

Gnomad4 OTH exome

AF:

0.00281

GnomAD4 genome

AF:

0.00124

AC:

188

AN:

152214

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.0331

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00266

Hom.:

Bravo

AF:

0.00131

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00142

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

9.8

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0095

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over