Genetic Variant RERG:p.Val95Val (chr12-15109425-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_032918.3(RERG):c.285G>A(p.Val95Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 1,614,044 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 49 hom. )

Consequence

RERG
NM_032918.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.123

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 12-15109425-C-T is Benign according to our data. Variant chr12-15109425-C-T is described in ClinVar as [Benign]. Clinvar id is 769816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.123 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERG	NM_032918.3 link	c.285G>A	p.Val95Val	synonymous_variant	Exon 5 of 5	ENST00000256953.6	NP_116307.1	Q96A58-1A0A024RAT4
RERG	NM_001190726.2 link	c.228G>A	p.Val76Val	synonymous_variant	Exon 4 of 4		NP_001177655.1	Q96A58-2
RERG	XM_047429797.1 link	c.276G>A	p.Val92Val	synonymous_variant	Exon 5 of 5		XP_047285753.1
RERG	XM_047429798.1 link	c.*139G>A		downstream_gene_variant			XP_047285754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERG	ENST00000256953.6 link	c.285G>A	p.Val95Val	synonymous_variant	Exon 5 of 5	1	NM_032918.3	ENSP00000256953.2		Q96A58-1

Frequencies

GnomAD3 genomes

AF:

0.00551

AC:

838

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000756

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00722

Gnomad OTH

AF:

0.00959

GnomAD2 exomes

AF:

0.00496

AC:

1247

AN:

251404

AF XY:

0.00506

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00501

Gnomad ASJ exome

AF:

0.0210

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000924

Gnomad NFE exome

AF:

0.00655

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00572

AC:

8362

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

4099

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.000836

AC:

AN:

33480

American (AMR)

AF:

0.00548

AC:

245

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0223

AC:

583

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00136

AC:

117

AN:

86250

European-Finnish (FIN)

AF:

0.000973

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00589

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00621

AC:

6909

AN:

1111974

Other (OTH)

AF:

0.00651

AC:

393

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

430

860

1291

1721

2151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00551

AC:

839

AN:

152206

Hom.:

Cov.:

AF XY:

0.00540

AC XY:

402

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

41538

American (AMR)

AF:

0.0110

AC:

168

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00290

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000756

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00722

AC:

491

AN:

68008

Other (OTH)

AF:

0.00996

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

123

164

205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00783

Hom.:

Bravo

AF:

0.00625

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00666

EpiControl

AF:

0.00759

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.35

CADD

Benign

3.7

(source)

DANN

Benign

0.76

PhyloP100

-0.12

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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12-15109425-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over