Variant rs868044 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001481.3(GAS8):c.595G>A(p.Glu199Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,612,348 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 33 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 236 hom. )

Consequence

GAS8
NM_001481.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 8.01

Variant links:

Genes affected

GAS8 (HGNC:4166): (growth arrest specific 8) This gene includes 11 exons spanning 25 kb and maps to a region of chromosome 16 that is sometimes deleted in breast and prostrate cancer. The second intron contains an apparently intronless gene, C16orf3, that is transcribed in the opposite orientation. This gene is a putative tumor suppressor gene. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

GAS8 links:

GAS8 (HGNC:):

GAS8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002479434).

BP6

Variant 16-90036425-G-A is Benign according to our data. Variant chr16-90036425-G-A is described in ClinVar as [Benign]. Clinvar id is 475567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS8	NM_001481.3 linkuse as main transcript	c.595G>A	p.Glu199Lys	missense_variant	6/11	ENST00000268699.9	NP_001472.1	O95995-1A0A384MR00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000268699.9 linkuse as main transcript	c.595G>A	p.Glu199Lys	missense_variant	6/11	1	NM_001481.3	ENSP00000268699.4		O95995-1

Frequencies

GnomAD3 genomes

AF:

0.00597

AC:

908

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0484

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.0150

AC:

3759

AN:

250638

Hom.:

205

AF XY:

0.0110

AC XY:

1491

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00218

Gnomad SAS exome

AF:

0.00236

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000415

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.00342

AC:

4992

AN:

1460030

Hom.:

236

Cov.:

AF XY:

0.00291

AC XY:

2114

AN XY:

726002

show subpopulations

Gnomad4 AFR exome

AF:

0.000957

Gnomad4 AMR exome

AF:

0.0956

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00182

Gnomad4 SAS exome

AF:

0.00235

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000221

Gnomad4 OTH exome

AF:

0.00280

GnomAD4 genome

AF:

0.00597

AC:

909

AN:

152318

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

499

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.0484

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00366

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.0117

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.0116

AC:

1408

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia 33

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.92

D;D;D

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-1.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.2

N;N;.

REVEL

Benign

0.24

Sift

Benign

0.15

T;T;.

Sift4G

Benign

0.34

T;T;T

Polyphen

0.28

.;B;.

Vest4

0.34

MPC

0.026

ClinPred

0.028

GERP RS

5.6

Varity_R

0.19

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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