rs2330411

Positions:

• chr7-42110248-T-A

Variant summary

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

The NM_000168.6(GLI3):​c.368-33391A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,196 control chromosomes in the GnomAD database, including 28,254 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 0.60 (28254 hom., cov: 33)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.567

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=-0.83).
• 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.368-33391A>T		intron_variant		ENST00000395925.8	NP_000159.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI3	ENST00000395925.8	c.368-33391A>T		intron_variant		5	NM_000168.6	ENSP00000379258	P1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90804 AN: 152076 Hom.: 28247 Cov.: 33

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.597 AC: 90833 AN: 152196 Hom.: 28254 Cov.: 33 AF XY: 0.596 AC XY: 44372 AN XY: 74432

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.603

Alfa AF: 0.619 Hom.: 3746

Bravo AF: 0.591

Asia WGS AF: 0.638 AC: 2218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.81

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: rs2330411; hg19: chr7-42149847;