rs10783827

Positions:

• chr12-57460528-G-T

Variant summary

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

The ENST00000228682.7(GLI1):​c.-28+327G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,334 control chromosomes in the GnomAD database, including 30,540 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 0.63 (30462 hom., cov: 30)
  • Exomes 𝑓: 0.58 (78 hom.)
• Consequence: GLI1 ENST00000228682.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

Genes affected

GLI1 (HGNC:4317): (GLI family zinc finger 1) This gene encodes a member of the Kruppel family of zinc finger proteins. The encoded transcription factor is activated by the sonic hedgehog signal transduction cascade and regulates stem cell proliferation. The activity and nuclear localization of this protein is negatively regulated by p53 in an inhibitory loop. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI1	NM_005269.3	c.-28+327G>T		intron_variant		ENST00000228682.7	NP_005260.1
LOC124902947	XR_007063335.1	n.231-967C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI1	ENST00000228682.7	c.-28+327G>T		intron_variant		1	NM_005269.3	ENSP00000228682	P1
	ENST00000656936.1	n.77-967C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95133 AN: 151748 Hom.: 30459 Cov.: 30

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.579 AC: 271 AN: 468 Hom.: 78 Cov.: 0 AF XY: 0.613 AC XY: 152 AN XY: 248

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.590

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.627 AC: 95163 AN: 151866 Hom.: 30462 Cov.: 30 AF XY: 0.615 AC XY: 45670 AN XY: 74206

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.646

Alfa AF: 0.675 Hom.: 36515

Bravo AF: 0.621

Asia WGS AF: 0.413 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10783827; hg19: chr12-57854311;