rs2049622

chr7-42136683-G-Achr7-42136683-G-C

Variant summary

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

The NM_000168.6(GLI3):c.367+11543C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,122 control chromosomes in the GnomAD database, including 17,098 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 0.46 (17098 hom., cov: 33)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI3	NM_000168.6	c.367+11543C>T		intron_variant		ENST00000395925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI3	ENST00000395925.8	c.367+11543C>T		intron_variant		5	NM_000168.6	P1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69381 AN: 152006 Hom.: 17102 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.456 AC: 69390 AN: 152122 Hom.: 17098 Cov.: 33 AF XY: 0.464 AC XY: 34540 AN XY: 74364

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.499

Alfa AF: 0.492 Hom.: 8842

Bravo AF: 0.443

Asia WGS AF: 0.656 AC: 2278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.52

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: rs2049622; hg19: chr7-42176282;