Variant 12-26065001-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001394098.1(RASSF8):c.607G>C(p.Glu203Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000825 in 1,613,008 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 7 hom. )

Consequence

RASSF8
NM_001394098.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.14

Variant links:

Genes affected

RASSF8 (HGNC:13232): (Ras association domain family member 8) This gene encodes a member of the Ras-assocation domain family (RASSF) of tumor suppressor proteins. This gene is essential for maintaining adherens junction function in epithelial cells and has a role in epithelial cell migration. It is a lung tumor suppressor gene candidate. A chromosomal translocation t(12;22)(p11.2;q13.3) leading to the fusion of this gene and the FBLN1 gene is found in a complex type of synpolydactyly. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

RASSF8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016749829).

BP6

Variant 12-26065001-G-C is Benign according to our data. Variant chr12-26065001-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 713622.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASSF8	NM_001394098.1 linkuse as main transcript	c.607G>C	p.Glu203Gln	missense_variant	4/6	ENST00000689635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASSF8	ENST00000689635.1 linkuse as main transcript	c.607G>C	p.Glu203Gln	missense_variant	4/6		NM_001394098.1	P1	Q8NHQ8-1

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

151

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000905

AC:

225

AN:

248606

Hom.:

AF XY:

0.000959

AC XY:

129

AN XY:

134564

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000299

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00147

Gnomad OTH exome

AF:

0.000992

GnomAD4 exome

AF:

0.000807

AC:

1179

AN:

1460704

Hom.:

Cov.:

AF XY:

0.000863

AC XY:

627

AN XY:

726624

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00234

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000221

Gnomad4 FIN exome

AF:

0.00144

Gnomad4 NFE exome

AF:

0.000873

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.000991

AC:

151

AN:

152304

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00173

Hom.:

Bravo

AF:

0.000593

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00105

AC:

128

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.018

.;T;.;T;T;T;.;T

Eigen

Benign

-0.046

Eigen_PC

Benign

0.068

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

T;.;.;.;T;T;D;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.017

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;L;L;L;.;.;L

MutationTaster

Benign

0.96

D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.38

N;N;.;N;N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.25

T;T;.;T;T;T;D;T

Sift4G

Benign

0.51

T;T;T;T;T;T;T;T

Polyphen

0.59

P;B;P;B;B;.;.;B

Vest4

0.36

MVP

0.48

MPC

0.20

ClinPred

0.24

GERP RS

4.0

Varity_R

0.10

gMVP

0.24

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

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