rs884928

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001481.3(GAS8):c.245G>A(p.Arg82Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00261 in 1,600,554 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 10 hom. )

Consequence

GAS8
NM_001481.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.62

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:

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=0.006713599).

BP6

Variant 16-90031453-G-A is Benign according to our data. Variant chr16-90031453-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00208 (317/152338) while in subpopulation AMR AF= 0.00301 (46/15306). AF 95% confidence interval is 0.00234. There are 0 homozygotes in gnomad4. There are 155 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS8	NM_001481.3 linkuse as main transcript	c.245G>A	p.Arg82Gln	missense_variant	3/11	ENST00000268699.9	NP_001472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000268699.9 linkuse as main transcript	c.245G>A	p.Arg82Gln	missense_variant	3/11	1	NM_001481.3	ENSP00000268699	P4	O95995-1

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

316

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00266

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00240

AC:

525

AN:

219044

Hom.:

AF XY:

0.00215

AC XY:

255

AN XY:

118582

show subpopulations

Gnomad AFR exome

AF:

0.000296

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.000449

Gnomad SAS exome

AF:

0.0000356

Gnomad FIN exome

AF:

0.000374

Gnomad NFE exome

AF:

0.00278

Gnomad OTH exome

AF:

0.00252

GnomAD4 exome

AF:

0.00266

AC:

3858

AN:

1448216

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

1849

AN XY:

719286

show subpopulations

Gnomad4 AFR exome

AF:

0.000241

Gnomad4 AMR exome

AF:

0.00117

Gnomad4 ASJ exome

AF:

0.0192

Gnomad4 EAS exome

AF:

0.000103

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000324

Gnomad4 NFE exome

AF:

0.00282

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00208

AC:

317

AN:

152338

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

155

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00266

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00343

Hom.:

Bravo

AF:

0.00215

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000684

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00179

AC:

216

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 33

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetics and Molecular Pathology, SA Pathology	Aug 27, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 20, 2024	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 08, 2020	- -

GAS8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

.;.;T

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.058

MetaRNN

Benign

0.0067

T;T;T

MetaSVM

Benign

-0.45

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.0070

D;T;D

Polyphen

1.0

.;.;D

Vest4

0.69

MVP

0.52

MPC

0.15

ClinPred

0.055

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.33

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