rs7785287

chr7-42051506-C-T

Variant summary

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

The NM_000168.6(GLI3):c.474-2810G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,052 control chromosomes in the GnomAD database, including 5,257 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 0.25 (5257 hom., cov: 32)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI3	NM_000168.6	c.474-2810G>A		intron_variant		ENST00000395925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI3	ENST00000395925.8	c.474-2810G>A		intron_variant		5	NM_000168.6	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37714 AN: 151934 Hom.: 5253 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.225

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.248 AC: 37736 AN: 152052 Hom.: 5257 Cov.: 32 AF XY: 0.246 AC XY: 18287 AN XY: 74342

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.225

Alfa AF: 0.226 Hom.: 1178

Bravo AF: 0.253

Asia WGS AF: 0.282 AC: 980 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.1
Dann	Benign	0.65

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: rs7785287; hg19: chr7-42091105;