rs10486730

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000168.6(GLI3):​c.1498-1523T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 152,286 control chromosomes in the GnomAD database, including 271 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 0.049 ( 271 hom., cov: 33)

Consequence

GLI3
NM_000168.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLI3NM_000168.6 linkuse as main transcriptc.1498-1523T>G intron_variant ENST00000395925.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLI3ENST00000395925.8 linkuse as main transcriptc.1498-1523T>G intron_variant 5 NM_000168.6 P1

Frequencies

GnomAD3 genomes
AF:
0.0490
AC:
7457
AN:
152168
Hom.:
270
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0945
Gnomad AMI
AF:
0.0603
Gnomad AMR
AF:
0.0330
Gnomad ASJ
AF:
0.0429
Gnomad EAS
AF:
0.00308
Gnomad SAS
AF:
0.0420
Gnomad FIN
AF:
0.0182
Gnomad MID
AF:
0.0633
Gnomad NFE
AF:
0.0339
Gnomad OTH
AF:
0.0460
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0490
AC:
7465
AN:
152286
Hom.:
271
Cov.:
33
AF XY:
0.0473
AC XY:
3524
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0944
Gnomad4 AMR
AF:
0.0329
Gnomad4 ASJ
AF:
0.0429
Gnomad4 EAS
AF:
0.00309
Gnomad4 SAS
AF:
0.0422
Gnomad4 FIN
AF:
0.0182
Gnomad4 NFE
AF:
0.0339
Gnomad4 OTH
AF:
0.0464
Alfa
AF:
0.0380
Hom.:
23
Bravo
AF:
0.0527
Asia WGS
AF:
0.0330
AC:
116
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
4.3
DANN
Benign
0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10486730; hg19: chr7-42019870; API