rs4760148

Variant names:

• chr12-57462993-C-G
• rs4760148
• NM_005269.3:c.-27-672C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-57462993-C-G
• chr12-57462993-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005269.3(GLI1):​c.-27-672C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,048 control chromosomes in the GnomAD database, including 23,103 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 0.53 (23103 hom., cov: 32)
• Consequence: GLI1 NM_005269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 6 publications found

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]

GLI1 Gene-Disease associations (from GenCC):

• Ellis-van Creveld syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• polydactyly of a biphalangeal thumb

  Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet
• postaxial polydactyly type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• polydactyly, postaxial, type A8

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000287200 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLI1	NM_005269.3	c.-27-672C>G		intron_variant	Intron 1 of 11	ENST00000228682.7	NP_005260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLI1	ENST00000228682.7	c.-27-672C>G		intron_variant	Intron 1 of 11	1	NM_005269.3	ENSP00000228682.2

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79989 AN: 151930 Hom.: 23105 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.526 AC: 79999 AN: 152048 Hom.: 23103 Cov.: 32 AF XY: 0.517 AC XY: 38438 AN XY: 74332

African (AFR) AF: 0.310 AC: 12860 AN: 41442

American (AMR) AF: 0.475 AC: 7254 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2317 AN: 3466

East Asian (EAS) AF: 0.325 AC: 1680 AN: 5176

South Asian (SAS) AF: 0.468 AC: 2252 AN: 4816

European-Finnish (FIN) AF: 0.553 AC: 5846 AN: 10578

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45805 AN: 67978

Other (OTH) AF: 0.570 AC: 1201 AN: 2108

Alfa AF: 0.577 Hom.: 3199

Bravo AF: 0.507

Asia WGS AF: 0.384 AC: 1336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4760148; hg19: chr12-57856776; COSMIC: COSV56989205; COSMIC: COSV56989205;