rs2073770

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_053004.3(GNB1L):c.715T>G(p.Trp239Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,593,300 control chromosomes in the GnomAD database, including 19,065 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1745 hom., cov: 33)

Exomes 𝑓: 0.13 ( 17320 hom. )

Consequence

GNB1L
NM_053004.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.93

Publications

22 publications found

Variant links:

Genes affected

GNB1L (HGNC:4397): (G protein subunit beta 1 like) This gene encodes a G-protein beta-subunit-like polypeptide which is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 6 WD repeats and is highly expressed in the heart. The gene maps to the region on chromosome 22q11, which is deleted in DiGeorge syndrome, trisomic in derivative 22 syndrome and tetrasomic in cat-eye syndrome. Therefore, this gene may contribute to the etiology of those disorders. Transcripts from this gene share exons with some transcripts from the C22orf29 gene. [provided by RefSeq, Jul 2008]

GNB1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016080439).

BP6

Variant 22-19802018-A-C is Benign according to our data. Variant chr22-19802018-A-C is described in ClinVar as Benign. ClinVar VariationId is 3060781.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1L	NM_053004.3 link	c.715T>G	p.Trp239Gly	missense_variant	Exon 7 of 8	ENST00000329517.11	NP_443730.1	Q9BYB4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB1L	ENST00000329517.11 link	c.715T>G	p.Trp239Gly	missense_variant	Exon 7 of 8	1	NM_053004.3	ENSP00000331313.6		Q9BYB4-1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18259

AN:

152184

Hom.:

1742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.0594

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.127

GnomAD2 exomes

AF:

0.176

AC:

37855

AN:

215230

AF XY:

0.174

show subpopulations

Gnomad AFR exome

AF:

0.0407

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.479

Gnomad FIN exome

AF:

0.0584

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.134

AC:

193182

AN:

1440998

Hom.:

17320

Cov.:

AF XY:

0.137

AC XY:

97822

AN XY:

715238

show subpopulations

African (AFR)

AF:

0.0402

AC:

1325

AN:

32994

American (AMR)

AF:

0.286

AC:

11788

AN:

41202

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

5233

AN:

25744

East Asian (EAS)

AF:

0.501

AC:

19276

AN:

38496

South Asian (SAS)

AF:

0.211

AC:

17656

AN:

83692

European-Finnish (FIN)

AF:

0.0605

AC:

3093

AN:

51140

Middle Eastern (MID)

AF:

0.155

AC:

869

AN:

5592

European-Non Finnish (NFE)

AF:

0.114

AC:

125387

AN:

1102480

Other (OTH)

AF:

0.143

AC:

8555

AN:

59658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

8876

17753

26629

35506

44382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4828

9656

14484

19312

24140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.120

AC:

18270

AN:

152302

Hom.:

1745

Cov.:

AF XY:

0.125

AC XY:

9307

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0432

AC:

1796

AN:

41570

American (AMR)

AF:

0.219

AC:

3344

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

739

AN:

3470

East Asian (EAS)

AF:

0.479

AC:

2475

AN:

5172

South Asian (SAS)

AF:

0.220

AC:

1062

AN:

4828

European-Finnish (FIN)

AF:

0.0594

AC:

631

AN:

10624

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7721

AN:

68020

Other (OTH)

AF:

0.125

AC:

264

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

799

1598

2397

3196

3995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.124

Hom.:

2145

Bravo

AF:

0.127

TwinsUK

AF:

0.113

AC:

418

ALSPAC

AF:

0.109

AC:

420

ESP6500AA

AF:

0.0391

AC:

172

ESP6500EA

AF:

0.113

AC:

968

ExAC

AF:

0.155

AC:

18662

Asia WGS

AF:

0.292

AC:

1016

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GNB1L-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.028

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.039

T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.017

.;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.4

N;N

PhyloP100

1.9

PrimateAI

Benign

0.24

PROVEAN

Benign

1.9

N;N

REVEL

Benign

0.058

Sift

Benign

0.54

T;T

Sift4G

Benign

0.80

T;T

Polyphen

0.0

B;B

Vest4

0.049

MPC

0.38

ClinPred

0.0010

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.079

gMVP

0.30

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over