rs10486730

Positions:

• chr7-41980271-A-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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=-0.83).
• 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
GLI3	NM_000168.6	c.1498-1523T>G		intron_variant		ENST00000395925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI3	ENST00000395925.8	c.1498-1523T>G		intron_variant		5	NM_000168.6	P1

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7457 AN: 152168 Hom.: 270 Cov.: 33

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

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

Other links and lift over

dbSNP: rs10486730; hg19: chr7-42019870;