1-53543606-C-G

Variant names:

• chr1-53543606-C-G
• rs496933
• NM_001367484.1:c.1321-13654G>C

Variant summary

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

The NM_001390836.1(GLIS1):​c.1345-13654G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,116 control chromosomes in the GnomAD database, including 35,959 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 0.68 (35959 hom., cov: 33)
• Consequence: GLIS1 NM_001390836.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 1 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 = 0.967 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001390836.1. 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
	GLIS1	NM_001367484.1	MANE Select	c.1321-13654G>C		intron	N/A	NP_001354413.1
	GLIS1	NM_001390836.1		c.1345-13654G>C		intron	N/A	NP_001377765.1
	GLIS1	NM_001390837.1		c.1321-13654G>C		intron	N/A	NP_001377766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIS1	ENST00000628545.2	TSL:5 MANE Select	c.1321-13654G>C		intron	N/A	ENSP00000486112.1
	GLIS1	ENST00000863985.1		c.1321-13654G>C		intron	N/A	ENSP00000534044.1
	GLIS1	ENST00000954872.1		c.1321-18719G>C		intron	N/A	ENSP00000624931.1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103860 AN: 151998 Hom.: 35921 Cov.: 33

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.683 AC: 103943 AN: 152116 Hom.: 35959 Cov.: 33 AF XY: 0.686 AC XY: 51007 AN XY: 74366

African (AFR) AF: 0.702 AC: 29118 AN: 41486

American (AMR) AF: 0.757 AC: 11582 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2101 AN: 3470

East Asian (EAS) AF: 0.990 AC: 5128 AN: 5182

South Asian (SAS) AF: 0.631 AC: 3037 AN: 4816

European-Finnish (FIN) AF: 0.642 AC: 6790 AN: 10574

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43881 AN: 67974

Other (OTH) AF: 0.706 AC: 1493 AN: 2114

Alfa AF: 0.569 Hom.: 1733

Bravo AF: 0.698

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.71
PhyloP100		-0.39
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: rs496933; hg19: chr1-54009279;