1-53712828-G-T

Variant names:

• chr1-53712828-G-T
• rs12080993
• NM_001367484.1:c.259+24978C>A

Variant summary

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

The NM_001367484.1(GLIS1):​c.259+24978C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,988 control chromosomes in the GnomAD database, including 4,252 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 0.23 (4252 hom., cov: 31)
• Consequence: GLIS1 NM_001367484.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS1	NM_001367484.1	c.259+24978C>A		intron_variant	Intron 2 of 10	ENST00000628545.2	NP_001354413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLIS1	ENST00000628545.2	c.259+24978C>A		intron_variant	Intron 2 of 10	5	NM_001367484.1	ENSP00000486112.1
GLIS1	ENST00000312233.4	c.-267+21076C>A		intron_variant	Intron 1 of 9	2		ENSP00000309653.2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35674 AN: 151870 Hom.: 4250 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.235 AC: 35697 AN: 151988 Hom.: 4252 Cov.: 31 AF XY: 0.230 AC XY: 17114 AN XY: 74292

African (AFR) AF: 0.277 AC: 11474 AN: 41438

American (AMR) AF: 0.215 AC: 3285 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1440 AN: 5152

South Asian (SAS) AF: 0.127 AC: 614 AN: 4816

European-Finnish (FIN) AF: 0.176 AC: 1862 AN: 10564

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15392 AN: 67954

Other (OTH) AF: 0.244 AC: 515 AN: 2110

Alfa AF: 0.156 Hom.: 378

Bravo AF: 0.244

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.44
DANN	Benign	0.53
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12080993; hg19: chr1-54178501;