rs3779152

Positions:

• chr7-42119344-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261

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]

ACMG classification

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
GLI3	NM_000168.6	c.367+28882T>C		intron_variant		ENST00000395925.8	NP_000159.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI3	ENST00000395925.8	c.367+28882T>C		intron_variant		5	NM_000168.6	ENSP00000379258.3

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33700 AN: 152034 Hom.: 4607 Cov.: 32

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

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

Other links and lift over

dbSNP: rs3779152; hg19: chr7-42158943;