rs2286294

Positions:

• chr7-42172250-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.125-23782T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,384 control chromosomes in the GnomAD database, including 16,900 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 0.47 (16900 hom., cov: 30)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI3	NM_000168.6	c.125-23782T>C		intron_variant		ENST00000395925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI3	ENST00000395925.8	c.125-23782T>C		intron_variant		5	NM_000168.6	P1
GLI3	ENST00000677605.1	c.125-23782T>C		intron_variant				P1
GLI3	ENST00000678429.1	c.125-23782T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70713 AN: 151262 Hom.: 16875 Cov.: 30

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.468 AC: 70778 AN: 151384 Hom.: 16900 Cov.: 30 AF XY: 0.462 AC XY: 34180 AN XY: 73914

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.421

Alfa AF: 0.463 Hom.: 20882

Bravo AF: 0.469

Asia WGS AF: 0.333 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.84
DANN	Benign	0.73

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: rs2286294; hg19: chr7-42211849;