rs6663966

chr1-53604340-C-T

Variant summary

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

The NM_001367484.1(GLIS1):c.260-4062G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,200 control chromosomes in the GnomAD database, including 54,052 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 0.80 (54052 hom., cov: 32)
• Consequence: GLIS1 NM_001367484.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382

Genes affected

GLIS1 (HGNC:29525): (GLIS family zinc finger 1) GLIS1 is a GLI (MIM 165220)-related Kruppel-like zinc finger protein that functions as an activator and repressor of transcription (Kim et al., 2002 [PubMed 12042312]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLIS1	NM_001367484.1	c.260-4062G>A		intron_variant		ENST00000628545.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLIS1	ENST00000628545.2	c.260-4062G>A		intron_variant		5	NM_001367484.1	P2
GLIS1	ENST00000312233.4	c.-266-4062G>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122416 AN: 152082 Hom.: 54046 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.805 AC: 122447 AN: 152200 Hom.: 54052 Cov.: 32 AF XY: 0.808 AC XY: 60096 AN XY: 74422

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.949

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.988

Gnomad4 OTH AF: 0.857

Alfa AF: 0.897 Hom.: 16343

Bravo AF: 0.775

Asia WGS AF: 0.739 AC: 2571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	15
Dann	Benign	0.84

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: rs6663966; hg19: chr1-54070013;