chr12-57465052-G-A

Position:

• chr12-57465052-G-A

Variant summary

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

The NM_005269.3(GLI1):​c.390-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 1,550,560 control chromosomes in the GnomAD database, including 266,910 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 0.48 (19418 hom., cov: 33)
  • Exomes 𝑓: 0.59 (247492 hom.)
• Consequence: GLI1 NM_005269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851

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]

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 (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI1	NM_005269.3	c.390-59G>A		intron_variant		ENST00000228682.7	NP_005260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI1	ENST00000228682.7	c.390-59G>A		intron_variant		1	NM_005269.3	ENSP00000228682.2

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72286 AN: 152024 Hom.: 19423 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.585 AC: 818085 AN: 1398418 Hom.: 247492 Cov.: 22 AF XY: 0.583 AC XY: 407805 AN XY: 699396

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.579

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.432

Gnomad4 FIN exome AF: 0.516

Gnomad4 NFE exome AF: 0.631

Gnomad4 OTH exome AF: 0.548

GnomAD4 genome AF: 0.475 AC: 72291 AN: 152142 Hom.: 19418 Cov.: 33 AF XY: 0.468 AC XY: 34827 AN XY: 74380

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.519

Alfa AF: 0.518 Hom.: 3150

Bravo AF: 0.454

Asia WGS AF: 0.359 AC: 1252 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	8.8
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3817474; hg19: chr12-57858835; COSMIC: COSV57358107; COSMIC: COSV57358107;