rs3801192

chr7-42121928-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.367+26298G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 152,104 control chromosomes in the GnomAD database, including 696 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 0.093 (696 hom., cov: 32)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI3	NM_000168.6	c.367+26298G>A		intron_variant		ENST00000395925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI3	ENST00000395925.8	c.367+26298G>A		intron_variant		5	NM_000168.6	P1

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14130 AN: 151986 Hom.: 693 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.0928

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0862

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0931 AC: 14164 AN: 152104 Hom.: 696 Cov.: 32 AF XY: 0.0904 AC XY: 6721 AN XY: 74342

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0876

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.0521

Gnomad4 FIN AF: 0.0928

Gnomad4 NFE AF: 0.0863

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0913 Hom.: 728

Bravo AF: 0.0941

Asia WGS AF: 0.0620 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	9.6
Dann	Benign	0.56

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: rs3801192; hg19: chr7-42161527;