chr7-42225080-T-C

Position:

• chr7-42225080-T-C

Variant summary

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

The NM_000168.6(GLI3):​c.-42-1785A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,160 control chromosomes in the GnomAD database, including 12,264 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 0.37 (12264 hom., cov: 33)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.954

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI3	NM_000168.6	c.-42-1785A>G		intron_variant		ENST00000395925.8	NP_000159.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI3	ENST00000395925.8	c.-42-1785A>G		intron_variant		5	NM_000168.6	ENSP00000379258.3

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55909 AN: 152042 Hom.: 12261 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.368 AC: 55923 AN: 152160 Hom.: 12264 Cov.: 33 AF XY: 0.379 AC XY: 28200 AN XY: 74368

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.369

Alfa AF: 0.417 Hom.: 17840

Bravo AF: 0.347

Asia WGS AF: 0.535 AC: 1857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.83

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: rs4724100; hg19: chr7-42264679;