12-57467043-T-C

Position:

• chr12-57467043-T-C

Variant summary

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

The NM_005269.3(GLI1):​c.913-290T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,032 control chromosomes in the GnomAD database, including 32,797 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 0.65 (32797 hom., cov: 31)
• Consequence: GLI1 NM_005269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI1	NM_005269.3	c.913-290T>C		intron_variant		ENST00000228682.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI1	ENST00000228682.7	c.913-290T>C		intron_variant		1	NM_005269.3	P1
GLI1	ENST00000528467.1	c.790-290T>C		intron_variant		1
GLI1	ENST00000543426.5	c.529-290T>C		intron_variant		5
GLI1	ENST00000546141.5	c.790-290T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98640 AN: 151914 Hom.: 32775 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.649 AC: 98701 AN: 152032 Hom.: 32797 Cov.: 31 AF XY: 0.637 AC XY: 47338 AN XY: 74314

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.651

Alfa AF: 0.673 Hom.: 69968

Bravo AF: 0.644

Asia WGS AF: 0.471 AC: 1640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.31

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: rs4760259; hg19: chr12-57860826;