rs3779152

Variant summary

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

The NM_000168.6(GLI3):​c.367+28882T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,150 control chromosomes in the GnomAD database, including 4,613 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 0.22 ( 4613 hom., cov: 32)

Consequence

GLI3
NM_000168.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.261
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=-0.91).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GLI3NM_000168.6 linkuse as main transcriptc.367+28882T>C intron_variant ENST00000395925.8 NP_000159.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GLI3ENST00000395925.8 linkuse as main transcriptc.367+28882T>C intron_variant 5 NM_000168.6 ENSP00000379258 P1

Frequencies

GnomAD3 genomes
AF:
0.222
AC:
33700
AN:
152034
Hom.:
4607
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0630
Gnomad AMI
AF:
0.214
Gnomad AMR
AF:
0.254
Gnomad ASJ
AF:
0.366
Gnomad EAS
AF:
0.264
Gnomad SAS
AF:
0.333
Gnomad FIN
AF:
0.332
Gnomad MID
AF:
0.351
Gnomad NFE
AF:
0.275
Gnomad OTH
AF:
0.233
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.222
AC:
33703
AN:
152150
Hom.:
4613
Cov.:
32
AF XY:
0.228
AC XY:
16957
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0628
Gnomad4 AMR
AF:
0.253
Gnomad4 ASJ
AF:
0.366
Gnomad4 EAS
AF:
0.264
Gnomad4 SAS
AF:
0.333
Gnomad4 FIN
AF:
0.332
Gnomad4 NFE
AF:
0.275
Gnomad4 OTH
AF:
0.239
Alfa
AF:
0.251
Hom.:
897
Bravo
AF:
0.207
Asia WGS
AF:
0.309
AC:
1073
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.93
DANN
Benign
0.44

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: rs3779152; hg19: chr7-42158943; API