rs4740788

Variant names:

• chr9-4481668-T-C
• rs4740788
• ENST00000818379.1:n.696+7960A>G

Variant summary

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

The ENST00000818379.1(ENSG00000306426):​n.696+7960A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,096 control chromosomes in the GnomAD database, including 2,318 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 0.16 (2318 hom., cov: 32)
• Consequence: ENSG00000306426 ENST00000818379.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 7 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000818379.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000306426	ENST00000818379.1		n.696+7960A>G		intron	N/A
	ENSG00000306426	ENST00000818380.1		n.377+8198A>G		intron	N/A
	ENSG00000306426	ENST00000818381.1		n.231+8198A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24633 AN: 151978 Hom.: 2314 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0760

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.162 AC: 24660 AN: 152096 Hom.: 2318 Cov.: 32 AF XY: 0.161 AC XY: 11961 AN XY: 74348

African (AFR) AF: 0.253 AC: 10507 AN: 41454

American (AMR) AF: 0.180 AC: 2747 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3468

East Asian (EAS) AF: 0.106 AC: 549 AN: 5176

South Asian (SAS) AF: 0.184 AC: 889 AN: 4822

European-Finnish (FIN) AF: 0.0760 AC: 805 AN: 10596

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8194 AN: 68000

Other (OTH) AF: 0.151 AC: 318 AN: 2112

Alfa AF: 0.138 Hom.: 2799

Bravo AF: 0.173

Asia WGS AF: 0.174 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.78
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs4740788; hg19: chr9-4481668;