rs2228225

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005269.3(GLI1):c.576G>A(p.Glu192Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,613,246 control chromosomes in the GnomAD database, including 278,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 19404 hom., cov: 32)

Exomes 𝑓: 0.59 ( 258808 hom. )

Consequence

GLI1
NM_005269.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.94

Publications

30 publications found

Variant links:

Genes affected

GLI1 (HGNC:4317): (GLI family zinc finger 1) This gene encodes a member of the Kruppel family of zinc finger proteins. The encoded transcription factor is activated by the sonic hedgehog signal transduction cascade and regulates stem cell proliferation. The activity and nuclear localization of this protein is negatively regulated by p53 in an inhibitory loop. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

GLI1 Gene-Disease associations (from GenCC):

Ellis-van Creveld syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
polydactyly of a biphalangeal thumb
Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet
postaxial polydactyly type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
polydactyly, postaxial, type A8
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GLI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 12-57465648-G-A is Benign according to our data. Variant chr12-57465648-G-A is described in ClinVar as Benign. ClinVar VariationId is 1277191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLI1	NM_005269.3 link	c.576G>A	p.Glu192Glu	synonymous_variant	Exon 6 of 12	ENST00000228682.7	NP_005260.1	P08151-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLI1	ENST00000228682.7 link	c.576G>A	p.Glu192Glu	synonymous_variant	Exon 6 of 12	1	NM_005269.3	ENSP00000228682.2		P08151-1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72248

AN:

151976

Hom.:

19409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.630

Gnomad OTH

AF:

0.524

GnomAD2 exomes

AF:

0.496

AC:

124507

AN:

251084

AF XY:

0.510

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.581

Gnomad EAS exome

AF:

0.292

Gnomad FIN exome

AF:

0.510

Gnomad NFE exome

AF:

0.626

Gnomad OTH exome

AF:

0.560

GnomAD4 exome

AF:

0.586

AC:

856022

AN:

1461152

Hom.:

258808

Cov.:

AF XY:

0.584

AC XY:

424434

AN XY:

726892

show subpopulations

African (AFR)

AF:

0.225

AC:

7542

AN:

33472

American (AMR)

AF:

0.336

AC:

15024

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

15124

AN:

26130

East Asian (EAS)

AF:

0.400

AC:

15876

AN:

39692

South Asian (SAS)

AF:

0.432

AC:

37265

AN:

86236

European-Finnish (FIN)

AF:

0.515

AC:

27529

AN:

53414

Middle Eastern (MID)

AF:

0.649

AC:

3743

AN:

5768

European-Non Finnish (NFE)

AF:

0.631

AC:

700786

AN:

1111368

Other (OTH)

AF:

0.549

AC:

33133

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

16923

33846

50769

67692

84615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18288

36576

54864

73152

91440

<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:

0.475

AC:

72253

AN:

152094

Hom.:

19404

Cov.:

AF XY:

0.468

AC XY:

34785

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.238

AC:

9874

AN:

41510

American (AMR)

AF:

0.435

AC:

6645

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

2012

AN:

3470

East Asian (EAS)

AF:

0.323

AC:

1671

AN:

5170

South Asian (SAS)

AF:

0.427

AC:

2059

AN:

4822

European-Finnish (FIN)

AF:

0.516

AC:

5453

AN:

10558

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.630

AC:

42802

AN:

67970

Other (OTH)

AF:

0.519

AC:

1093

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1764

3528

5293

7057

8821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.569

Hom.:

65413

Bravo

AF:

0.454

Asia WGS

AF:

0.359

AC:

1252

AN:

3478

EpiCase

AF:

0.639

EpiControl

AF:

0.641

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 21, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

GLI1-related disorder

Benign:1

Aug 30, 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). -

Polydactyly, postaxial, type A8

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Polydactyly of a biphalangeal thumb

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.2

(source)

DANN

Benign

0.42

PhyloP100

1.9

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

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