rs6476866

Variant names:

• chr9-4459274-G-A
• rs6476866
• ENST00000818379.1:n.697-27433C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-4459274-G-A
• chr9-4459274-G-C

Variant summary

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

The ENST00000818379.1(ENSG00000306426):​n.697-27433C>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: ENSG00000306426 ENST00000818379.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 2 publications found

Genes affected

ENSG00000306426 (HGNC:):

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]

GLIS3 Gene-Disease associations (from GenCC):

• neonatal diabetes mellitus with congenital hypothyroidism

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Tourette syndrome

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GLIS3	XM_047422890.1	c.-152+30354C>T		intron_variant	Intron 1 of 11		XP_047278846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000306426	ENST00000818379.1	n.697-27433C>T		intron_variant	Intron 1 of 1
ENSG00000306426	ENST00000818380.1	n.378-27433C>T		intron_variant	Intron 1 of 1
ENSG00000306426	ENST00000818381.1	n.232-25850C>T		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.454 AC: 18800 AN: 41390

American (AMR) AF: 0.570 AC: 8700 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1883 AN: 3468

East Asian (EAS) AF: 0.501 AC: 2588 AN: 5168

South Asian (SAS) AF: 0.707 AC: 3403 AN: 4814

European-Finnish (FIN) AF: 0.572 AC: 6025 AN: 10534

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40997 AN: 67956

Other (OTH) AF: 0.548 AC: 1155 AN: 2108

Alfa AF: 0.594 Hom.: 15688

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
PhyloP100		-0.23

Splicing

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

Other links and lift over

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