rs2237425

chr7-42027757-C-Gchr7-42027757-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000168.6(GLI3):c.1029-1345G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,168 control chromosomes in the GnomAD database, including 1,858 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 0.14 (1858 hom., cov: 32)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI3	NM_000168.6	c.1029-1345G>C		intron_variant		ENST00000395925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI3	ENST00000395925.8	c.1029-1345G>C		intron_variant		5	NM_000168.6	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20956 AN: 152050 Hom.: 1859 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.138 AC: 20956 AN: 152168 Hom.: 1858 Cov.: 32 AF XY: 0.141 AC XY: 10451 AN XY: 74366

Gnomad4 AFR AF: 0.0424

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.150

Alfa AF: 0.140 Hom.: 228

Bravo AF: 0.130

Asia WGS AF: 0.262 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	16
Dann	Benign	0.71

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: rs2237425; hg19: chr7-42067356;