chr9-4459274-G-A

Position:

• chr9-4459274-G-A

Variant summary

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

The XM_047422890.1(GLIS3):​c.-152+30354C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,908 control chromosomes in the GnomAD database, including 23,821 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 0.55 (23821 hom., cov: 31)
• Consequence: GLIS3 XM_047422890.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

Genes affected

GLIS3 (HGNC:28510): (GLIS family zinc finger 3) This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear protein with five C2H2-type zinc finger domains. This protein functions as both a repressor and activator of transcription and is specifically involved in the development of pancreatic beta cells, the thyroid, eye, liver and kidney. Mutations in this gene have been associated with neonatal diabetes and congenital hypothyroidism (NDH). Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only two have been determined. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS3	XM_047422890.1	c.-152+30354C>T		intron_variant			XP_047278846.1
		n.4459274G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84150 AN: 151790 Hom.: 23801 Cov.: 31

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.554 AC: 84221 AN: 151908 Hom.: 23821 Cov.: 31 AF XY: 0.557 AC XY: 41328 AN XY: 74230

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.548

Alfa AF: 0.595 Hom.: 14388

Bravo AF: 0.545

Asia WGS AF: 0.617 AC: 2146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.040
DANN	Benign	0.13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6476866; hg19: chr9-4459274; COSMIC: COSV69444200;