rs846273

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000168.6(GLI3):c.1356+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 1,582,426 control chromosomes in the GnomAD database, including 752,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71959 hom., cov: 31)

Exomes 𝑓: 0.98 ( 680206 hom. )

Consequence

GLI3
NM_000168.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.305

Publications

7 publications found

Variant links:

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 7-42025253-C-G is Benign according to our data. Variant chr7-42025253-C-G is described in ClinVar as Benign. ClinVar VariationId is 255420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 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.1356+11G>C		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.1356+11G>C	intron	N/A	ENSP00000379258.3	P10071
GLI3	ENST00000677605.1		c.1356+11G>C	intron	N/A	ENSP00000503743.1	P10071
GLI3	ENST00000678429.1		c.1356+11G>C	intron	N/A	ENSP00000502957.1	P10071

Frequencies

GnomAD3 genomes

AF:

0.972

AC:

147926

AN:

152192

Hom.:

71902

Cov.:

show subpopulations

Gnomad AFR

AF:

0.959

Gnomad AMI

AF:

0.985

Gnomad AMR

AF:

0.981

Gnomad ASJ

AF:

0.962

Gnomad EAS

AF:

0.986

Gnomad SAS

AF:

0.955

Gnomad FIN

AF:

0.995

Gnomad MID

AF:

0.915

Gnomad NFE

AF:

0.975

Gnomad OTH

AF:

0.972

GnomAD2 exomes

AF:

0.975

AC:

244600

AN:

250862

AF XY:

0.974

show subpopulations

Gnomad AFR exome

AF:

0.960

Gnomad AMR exome

AF:

0.988

Gnomad ASJ exome

AF:

0.963

Gnomad EAS exome

AF:

0.985

Gnomad FIN exome

AF:

0.994

Gnomad NFE exome

AF:

0.974

Gnomad OTH exome

AF:

0.975

GnomAD4 exome

AF:

0.975

AC:

1394704

AN:

1430116

Hom.:

680206

Cov.:

AF XY:

0.975

AC XY:

695273

AN XY:

713352

show subpopulations

African (AFR)

AF:

0.955

AC:

31421

AN:

32890

American (AMR)

AF:

0.987

AC:

44128

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.962

AC:

24994

AN:

25982

East Asian (EAS)

AF:

0.986

AC:

38987

AN:

39558

South Asian (SAS)

AF:

0.957

AC:

81909

AN:

85612

European-Finnish (FIN)

AF:

0.993

AC:

52755

AN:

53122

Middle Eastern (MID)

AF:

0.933

AC:

5257

AN:

5634

European-Non Finnish (NFE)

AF:

0.976

AC:

1057528

AN:

1083354

Other (OTH)

AF:

0.974

AC:

57725

AN:

59272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1834

3669

5503

7338

9172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20896

41792

62688

83584

104480

<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:

0.972

AC:

148042

AN:

152310

Hom.:

71959

Cov.:

AF XY:

0.973

AC XY:

72498

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.959

AC:

39869

AN:

41564

American (AMR)

AF:

0.981

AC:

15022

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.962

AC:

3340

AN:

3472

East Asian (EAS)

AF:

0.986

AC:

5087

AN:

5158

South Asian (SAS)

AF:

0.955

AC:

4610

AN:

4828

European-Finnish (FIN)

AF:

0.995

AC:

10571

AN:

10626

Middle Eastern (MID)

AF:

0.915

AC:

269

AN:

294

European-Non Finnish (NFE)

AF:

0.975

AC:

66319

AN:

68032

Other (OTH)

AF:

0.972

AC:

2057

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

223

445

668

890

1113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.975

Hom.:

7657

Bravo

AF:

0.971

Asia WGS

AF:

0.966

AC:

3359

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Greig cephalopolysyndactyly syndrome (2)

not provided (2)

Pallister-Hall syndrome (2)

Pallister-Hall syndrome;C0265306:Greig cephalopolysyndactyly syndrome (1)

Polydactyly (1)

Polydactyly, postaxial, type A1 (1)

Polysyndactyly 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.044

(source)

DANN

Benign

0.37

PhyloP100

0.30

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