7-42113257-G-A

Position:

• chr7-42113257-G-A

Variant summary

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

The NM_000168.6(GLI3):​c.367+34969C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 508,554 control chromosomes in the GnomAD database, including 2,255 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 0.11 (922 hom., cov: 31)
  • Exomes 𝑓: 0.082 (1333 hom.)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621

Genes affected

GLI3 (HGNC:4319): (GLI family zinc finger 3) This gene encodes a protein which belongs to the C2H2-type zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding transcription factors and are mediators of Sonic hedgehog (Shh) signaling. The protein encoded by this gene localizes in the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis. Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI3	NM_000168.6	c.367+34969C>T		intron_variant		ENST00000395925.8	NP_000159.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI3	ENST00000395925.8	c.367+34969C>T		intron_variant		5	NM_000168.6	ENSP00000379258	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16038 AN: 151994 Hom.: 921 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0821 AC: 29258 AN: 356442 Hom.: 1333 AF XY: 0.0796 AC XY: 15900 AN XY: 199802

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0621

Gnomad4 ASJ exome AF: 0.0666

Gnomad4 EAS exome AF: 0.0116

Gnomad4 SAS exome AF: 0.0525

Gnomad4 FIN exome AF: 0.0910

Gnomad4 NFE exome AF: 0.0938

Gnomad4 OTH exome AF: 0.0920

GnomAD4 genome AF: 0.106 AC: 16058 AN: 152112 Hom.: 922 Cov.: 31 AF XY: 0.101 AC XY: 7534 AN XY: 74364

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0847

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.00850

Gnomad4 SAS AF: 0.0561

Gnomad4 FIN AF: 0.0894

Gnomad4 NFE AF: 0.0936

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0952 Hom.: 1277

Bravo AF: 0.109

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.5
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs6463089; hg19: chr7-42152856; COSMIC: COSV67894337; COSMIC: COSV67894337;