chr16-90037308-G-A

Position:

chr16-90037308-G-A

Variant summary

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

The NM_001481.3(GAS8):c.833G>A(p.Arg278His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,614,006 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 8 hom., cov: 33)

Exomes 𝑓: 0.011 ( 118 hom. )

Consequence

GAS8
NM_001481.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.74

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=0.0066363215).

BP6

Variant 16-90037308-G-A is Benign according to our data. Variant chr16-90037308-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-90037308-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00765 (1166/152324) while in subpopulation NFE AF= 0.0134 (911/68024). AF 95% confidence interval is 0.0127. There are 8 homozygotes in gnomad4. There are 566 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS8	NM_001481.3 linkuse as main transcript	c.833G>A	p.Arg278His	missense_variant	7/11	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.833G>A	p.Arg278His	missense_variant	7/11	1	NM_001481.3	ENSP00000268699.4		O95995-1

Frequencies

GnomAD3 genomes

AF:

0.00765

AC:

1165

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00207

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0134

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00768

AC:

1926

AN:

250726

Hom.:

AF XY:

0.00782

AC XY:

1060

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.00284

Gnomad ASJ exome

AF:

0.000597

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00573

Gnomad FIN exome

AF:

0.00472

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.00670

GnomAD4 exome

AF:

0.0108

AC:

15840

AN:

1461682

Hom.:

118

Cov.:

AF XY:

0.0108

AC XY:

7839

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00271

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00601

Gnomad4 FIN exome

AF:

0.00489

Gnomad4 NFE exome

AF:

0.0129

Gnomad4 OTH exome

AF:

0.00793

GnomAD4 genome

AF:

0.00765

AC:

1166

AN:

152324

Hom.:

Cov.:

AF XY:

0.00760

AC XY:

566

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.00490

Gnomad4 NFE

AF:

0.0134

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00697

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0158

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0119

AC:

102

ExAC

AF:

0.00845

AC:

1026

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0113

EpiControl

AF:

0.0107

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	GAS8: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2020	- -

Primary ciliary dyskinesia 33

Benign:2

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 18, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.085

.;T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.89

D;D;D

MetaRNN

Benign

0.0066

T;T;T

MetaSVM

Benign

-0.39

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.9

D;D;.

REVEL

Benign

0.096

Sift

Uncertain

0.0030

D;D;.

Sift4G

Uncertain

0.010

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.18

MVP

0.63

MPC

0.036

ClinPred

0.027

GERP RS

4.5

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.22

gMVP

0.17

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