rs145962792

Positions:

chr16-90040361-A-G

Variant summary

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

The ENST00000268699.9(GAS8):c.1073A>G(p.Gln358Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00223 in 1,608,366 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 6 hom. )

Consequence

GAS8
ENST00000268699.9 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.17

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:

URAHP (HGNC:43695): (urate (hydroxyiso-) hydrolase, pseudogene) Predicted to enable hydroxyisourate hydrolase activity. Predicted to be involved in allantoin metabolic process; purine-containing compound catabolic process; and urate catabolic process. Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

URAHP 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=0.010979295).

BP6

Variant 16-90040361-A-G is Benign according to our data. Variant chr16-90040361-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 542269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00167 (254/152366) while in subpopulation NFE AF= 0.00253 (172/68034). AF 95% confidence interval is 0.00222. There are 0 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS8	NM_001481.3 linkuse as main transcript	c.1073A>G	p.Gln358Arg	missense_variant	9/11	ENST00000268699.9	NP_001472.1
URAHP	NR_027335.2 linkuse as main transcript	n.749T>C		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000268699.9 linkuse as main transcript	c.1073A>G	p.Gln358Arg	missense_variant	9/11	1	NM_001481.3	ENSP00000268699	P4	O95995-1
URAHP	ENST00000409873.5 linkuse as main transcript	n.749T>C		non_coding_transcript_exon_variant	5/5	1

Frequencies

GnomAD3 genomes

AF:

0.00167

AC:

254

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00140

AC:

334

AN:

238878

Hom.:

AF XY:

0.00140

AC XY:

181

AN XY:

129342

show subpopulations

Gnomad AFR exome

AF:

0.000794

Gnomad AMR exome

AF:

0.000297

Gnomad ASJ exome

AF:

0.00838

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000992

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00229

AC:

3332

AN:

1456000

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

1614

AN XY:

723672

show subpopulations

Gnomad4 AFR exome

AF:

0.000360

Gnomad4 AMR exome

AF:

0.000204

Gnomad4 ASJ exome

AF:

0.00858

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000945

Gnomad4 NFE exome

AF:

0.00268

Gnomad4 OTH exome

AF:

0.00186

GnomAD4 genome

AF:

0.00167

AC:

254

AN:

152366

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00253

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00246

Hom.:

Bravo

AF:

0.00173

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00125

AC:

151

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

GAS8-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 2019

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

Primary ciliary dyskinesia 33

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.45

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.7

D;D;.

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D;.

Sift4G

Uncertain

0.013

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.50

MVP

0.58

MPC

0.15

ClinPred

0.064

GERP RS

5.8

Varity_R

0.85

gMVP

0.41

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