rs3779162

Variant names:

• chr7-42166335-G-A
• rs3779162
• NM_000168.6:c.125-17867C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-42166335-G-A
• chr7-42166335-G-C
• chr7-42166335-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000168.6(GLI3):​c.125-17867C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 152,282 control chromosomes in the GnomAD database, including 289 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 0.061 (289 hom., cov: 32)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922
• Publications: 1 publications found

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]

GLI3 Gene-Disease associations (from GenCC):

• Greig cephalopolysyndactyly syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics, PanelApp Australia
• Pallister-Hall syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Ambry Genetics, Orphanet
• polydactyly, postaxial, type A1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• polysyndactyly 4

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• tibial hemimelia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• acrocallosal syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• postaxial polydactyly type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000168.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLI3	NM_000168.6	MANE Select	c.125-17867C>T		intron	N/A	NP_000159.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLI3	ENST00000395925.8	TSL:5 MANE Select	c.125-17867C>T		intron	N/A	ENSP00000379258.3
	GLI3	ENST00000677605.1		c.125-17867C>T		intron	N/A	ENSP00000503743.1
	GLI3	ENST00000678429.1		c.125-17867C>T		intron	N/A	ENSP00000502957.1

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9331 AN: 152164 Hom.: 288 Cov.: 32

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.00905

Gnomad SAS AF: 0.0629

Gnomad FIN AF: 0.0566

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.0565

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

GnomAD4 genome AF: 0.0613 AC: 9340 AN: 152282 Hom.: 289 Cov.: 32 AF XY: 0.0621 AC XY: 4621 AN XY: 74464

African (AFR) AF: 0.0586 AC: 2435 AN: 41544

American (AMR) AF: 0.107 AC: 1641 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3470

East Asian (EAS) AF: 0.00907 AC: 47 AN: 5184

South Asian (SAS) AF: 0.0634 AC: 306 AN: 4828

European-Finnish (FIN) AF: 0.0566 AC: 600 AN: 10608

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0591 AC: 4022 AN: 68032

Other (OTH) AF: 0.0559 AC: 118 AN: 2110

Alfa AF: 0.0424 Hom.: 73

Bravo AF: 0.0666

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.40
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3779162; hg19: chr7-42205934;