Variant 12-57465648-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000228682.7(GLI1):c.576G>A(p.Glu192=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,613,246 control chromosomes in the GnomAD database, including 278,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 19404 hom., cov: 32)

Exomes 𝑓: 0.59 ( 258808 hom. )

Consequence

GLI1
ENST00000228682.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.94

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 12-57465648-G-A is Benign according to our data. Variant chr12-57465648-G-A is described in ClinVar as [Benign]. Clinvar id is 1277191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI1	NM_005269.3 linkuse as main transcript	c.576G>A	p.Glu192=	synonymous_variant	6/12	ENST00000228682.7	NP_005260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI1	ENST00000228682.7 linkuse as main transcript	c.576G>A	p.Glu192=	synonymous_variant	6/12	1	NM_005269.3	ENSP00000228682	P1	P08151-1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72248

AN:

151976

Hom.:

19409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.630

Gnomad OTH

AF:

0.524

GnomAD3 exomes

AF:

0.496

AC:

124507

AN:

251084

Hom.:

33772

AF XY:

0.510

AC XY:

69158

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.581

Gnomad EAS exome

AF:

0.292

Gnomad SAS exome

AF:

0.429

Gnomad FIN exome

AF:

0.510

Gnomad NFE exome

AF:

0.626

Gnomad OTH exome

AF:

0.560

GnomAD4 exome

AF:

0.586

AC:

856022

AN:

1461152

Hom.:

258808

Cov.:

AF XY:

0.584

AC XY:

424434

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.336

Gnomad4 ASJ exome

AF:

0.579

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.432

Gnomad4 FIN exome

AF:

0.515

Gnomad4 NFE exome

AF:

0.631

Gnomad4 OTH exome

AF:

0.549

GnomAD4 genome

AF:

0.475

AC:

72253

AN:

152094

Hom.:

19404

Cov.:

AF XY:

0.468

AC XY:

34785

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.435

Gnomad4 ASJ

AF:

0.580

Gnomad4 EAS

AF:

0.323

Gnomad4 SAS

AF:

0.427

Gnomad4 FIN

AF:

0.516

Gnomad4 NFE

AF:

0.630

Gnomad4 OTH

AF:

0.519

Alfa

AF:

0.590

Hom.:

46537

Bravo

AF:

0.454

Asia WGS

AF:

0.359

AC:

1252

AN:

3478

EpiCase

AF:

0.639

EpiControl

AF:

0.641

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 21, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

GLI1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Polydactyly, postaxial, type A8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Polydactyly of a biphalangeal thumb

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.2

DANN

Benign

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over