dbSNP rs10783827: GLI1:n.16G>T (chr12-57460528-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000530789.1(GLI1):n.16G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,334 control chromosomes in the GnomAD database, including 30,540 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.63 ( 30462 hom., cov: 30)

Exomes 𝑓: 0.58 ( 78 hom. )

Consequence

GLI1
ENST00000530789.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

Publications

15 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:

ENSG00000287200 (HGNC:):

ENSG00000287200 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLI1	NM_005269.3 link	c.-28+327G>T		intron_variant	Intron 1 of 11	ENST00000228682.7	NP_005260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLI1	ENST00000228682.7 link	c.-28+327G>T		intron_variant	Intron 1 of 11	1	NM_005269.3	ENSP00000228682.2

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95133

AN:

151748

Hom.:

30459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.635

Gnomad AMI

AF:

0.746

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.679

Gnomad OTH

AF:

0.653

GnomAD4 exome

AF:

0.579

AC:

271

AN:

468

Hom.:

Cov.:

AF XY:

0.613

AC XY:

152

AN XY:

248

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.375

AC:

AN:

European-Finnish (FIN)

AF:

0.590

AC:

216

AN:

366

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.557

AC:

AN:

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.548

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.627

AC:

95163

AN:

151866

Hom.:

30462

Cov.:

AF XY:

0.615

AC XY:

45670

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.635

AC:

26264

AN:

41382

American (AMR)

AF:

0.521

AC:

7940

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.722

AC:

2504

AN:

3470

East Asian (EAS)

AF:

0.318

AC:

1639

AN:

5152

South Asian (SAS)

AF:

0.504

AC:

2427

AN:

4816

European-Finnish (FIN)

AF:

0.569

AC:

6003

AN:

10546

Middle Eastern (MID)

AF:

0.796

AC:

234

AN:

294

European-Non Finnish (NFE)

AF:

0.679

AC:

46116

AN:

67950

Other (OTH)

AF:

0.646

AC:

1356

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1738

3477

5215

6954

8692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<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:

0.674

Hom.:

50173

Bravo

AF:

0.621

Asia WGS

AF:

0.413

AC:

1440

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

1.7

PromoterAI

0.0098

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over