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GeneBe

12-15121064-G-A

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

2
Splicing: ADA: 0.009486
2

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.967 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 12 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RERGNM_032918.3 linkuse as main transcriptc.117C>T p.Leu39= splice_region_variant, synonymous_variant 3/5 ENST00000256953.6
RERGXM_047429797.1 linkuse as main transcriptc.108C>T p.Leu36= splice_region_variant, synonymous_variant 3/5
RERGXM_047429798.1 linkuse as main transcriptc.117C>T p.Leu39= splice_region_variant, synonymous_variant 3/6
RERGNM_001190726.2 linkuse as main transcriptc.62-9647C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RERGENST00000256953.6 linkuse as main transcriptc.117C>T p.Leu39= splice_region_variant, synonymous_variant 3/51 NM_032918.3 P1Q96A58-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00124
AC:
188
AN:
152096
Hom.:
0
Cov.:
32
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.:
12
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.:
19
Cov.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00124
AC:
188
AN:
152214
Hom.:
0
Cov.:
32
AF XY:
0.00109
AC XY:
81
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.:
14
Bravo
AF:
0.00131
Asia WGS
AF:
0.000289
AC:
1
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 submitterclinical testingInvitaeDec 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.

Other links and lift over

dbSNP: rs148630934; hg19: chr12-15273998; COSMIC: COSV57005979; COSMIC: COSV57005979; API