rs17707162

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000168.6(GLI3):c.1498-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 1,577,504 control chromosomes in the GnomAD database, including 6,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.087 ( 662 hom., cov: 33)

Exomes 𝑓: 0.085 ( 5625 hom. )

Consequence

GLI3
NM_000168.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.487

Publications

6 publications found

Variant links:

COSMIC-nc: COSV67886504

Genes affected

GLI3 (HGNC:4319): (GLI family zinc finger 3) This gene encodes a protein which belongs to the C2H2-type zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding transcription factors and are mediators of Sonic hedgehog (Shh) signaling. The protein encoded by this gene localizes in the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis. Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B. [provided by RefSeq, Jul 2008]

GLI3 Gene-Disease associations (from GenCC):

Greig cephalopolysyndactyly syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet, Laboratory for Molecular Medicine, G2P
Pallister-Hall syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
polydactyly, postaxial, type A1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
polysyndactyly 4
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
tibial hemimelia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
acrocallosal syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
postaxial polydactyly type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

GLI3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 7-41978792-C-T is Benign according to our data. Variant chr7-41978792-C-T is described in ClinVar as Benign. ClinVar VariationId is 255423.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000168.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLI3	NM_000168.6	MANE Select	c.1498-44G>A		intron	N/A	NP_000159.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLI3	ENST00000395925.8	TSL:5 MANE Select	c.1498-44G>A	intron	N/A	ENSP00000379258.3	P10071
GLI3	ENST00000677605.1		c.1498-44G>A	intron	N/A	ENSP00000503743.1	P10071
GLI3	ENST00000678429.1		c.1498-44G>A	intron	N/A	ENSP00000502957.1	P10071

Frequencies

GnomAD3 genomes

AF:

0.0870

AC:

13231

AN:

152104

Hom.:

661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.0629

Gnomad ASJ

AF:

0.0882

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.0707

Gnomad FIN

AF:

0.0487

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0868

Gnomad OTH

AF:

0.0894

GnomAD2 exomes

AF:

0.0714

AC:

17783

AN:

249120

AF XY:

0.0733

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.0461

Gnomad ASJ exome

AF:

0.0879

Gnomad EAS exome

AF:

0.00181

Gnomad FIN exome

AF:

0.0518

Gnomad NFE exome

AF:

0.0832

Gnomad OTH exome

AF:

0.0782

GnomAD4 exome

AF:

0.0852

AC:

121411

AN:

1425282

Hom.:

5625

Cov.:

AF XY:

0.0851

AC XY:

60558

AN XY:

711314

show subpopulations

African (AFR)

AF:

0.116

AC:

3806

AN:

32800

American (AMR)

AF:

0.0482

AC:

2150

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.0870

AC:

2256

AN:

25930

East Asian (EAS)

AF:

0.00207

AC:

AN:

39540

South Asian (SAS)

AF:

0.0794

AC:

6782

AN:

85438

European-Finnish (FIN)

AF:

0.0532

AC:

2828

AN:

53148

Middle Eastern (MID)

AF:

0.0803

AC:

457

AN:

5694

European-Non Finnish (NFE)

AF:

0.0908

AC:

98021

AN:

1079012

Other (OTH)

AF:

0.0851

AC:

5029

AN:

59120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

4921

9842

14763

19684

24605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3624

7248

10872

14496

18120

<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:

0.0870

AC:

13241

AN:

152222

Hom.:

662

Cov.:

AF XY:

0.0833

AC XY:

6200

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.118

AC:

4892

AN:

41512

American (AMR)

AF:

0.0628

AC:

961

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0882

AC:

306

AN:

3470

East Asian (EAS)

AF:

0.00329

AC:

AN:

5174

South Asian (SAS)

AF:

0.0705

AC:

340

AN:

4820

European-Finnish (FIN)

AF:

0.0487

AC:

517

AN:

10608

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0868

AC:

5904

AN:

68014

Other (OTH)

AF:

0.0894

AC:

189

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

625

1251

1876

2502

3127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0808

Hom.:

223

Bravo

AF:

0.0894

Asia WGS

AF:

0.0550

AC:

193

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.2

(source)

DANN

Benign

0.78

PhyloP100

0.49

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over