dbSNP rs6463089: GLI3:c.367+34969C>T (chr7-42113257-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000168.6(GLI3):c.367+34969C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 508,554 control chromosomes in the GnomAD database, including 2,255 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 0.11 ( 922 hom., cov: 31)

Exomes 𝑓: 0.082 ( 1333 hom. )

Consequence

GLI3
NM_000168.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.621

Publications

10 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 links:

HMGN2P30 (HGNC:39397): (high mobility group nucleosomal binding domain 2 pseudogene 30)

HMGN2P30 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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLI3	NM_000168.6 link	c.367+34969C>T		intron_variant	Intron 3 of 14	ENST00000395925.8	NP_000159.3	P10071

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLI3	ENST00000395925.8 link	c.367+34969C>T		intron_variant	Intron 3 of 14	5	NM_000168.6	ENSP00000379258.3		P10071

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16038

AN:

151994

Hom.:

921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.0845

Gnomad ASJ

AF:

0.0637

Gnomad EAS

AF:

0.00848

Gnomad SAS

AF:

0.0565

Gnomad FIN

AF:

0.0894

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0936

Gnomad OTH

AF:

0.106

GnomAD4 exome

AF:

0.0821

AC:

29258

AN:

356442

Hom.:

1333

AF XY:

0.0796

AC XY:

15900

AN XY:

199802

show subpopulations

African (AFR)

AF:

0.158

AC:

1594

AN:

10072

American (AMR)

AF:

0.0621

AC:

1651

AN:

26568

Ashkenazi Jewish (ASJ)

AF:

0.0666

AC:

804

AN:

12076

East Asian (EAS)

AF:

0.0116

AC:

163

AN:

14064

South Asian (SAS)

AF:

0.0525

AC:

3042

AN:

57974

European-Finnish (FIN)

AF:

0.0910

AC:

1635

AN:

17964

Middle Eastern (MID)

AF:

0.0793

AC:

170

AN:

2144

European-Non Finnish (NFE)

AF:

0.0938

AC:

18522

AN:

197358

Other (OTH)

AF:

0.0920

AC:

1677

AN:

18222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1426

2852

4279

5705

7131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<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:

0.106

AC:

16058

AN:

152112

Hom.:

922

Cov.:

AF XY:

0.101

AC XY:

7534

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.158

AC:

6573

AN:

41474

American (AMR)

AF:

0.0847

AC:

1295

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0637

AC:

221

AN:

3468

East Asian (EAS)

AF:

0.00850

AC:

AN:

5178

South Asian (SAS)

AF:

0.0561

AC:

269

AN:

4794

European-Finnish (FIN)

AF:

0.0894

AC:

947

AN:

10598

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0936

AC:

6363

AN:

68006

Other (OTH)

AF:

0.106

AC:

223

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

746

1492

2239

2985

3731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.0992

Hom.:

2307

Bravo

AF:

0.109

Asia WGS

AF:

0.0540

AC:

190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.5

(source)

DANN

Benign

0.89

PhyloP100

-0.62

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

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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