chr1-53572863-C-A

Variant names:

• chr1-53572863-C-A
• rs10493174
• NM_001367484.1:c.1320+21245G>T

Variant summary

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

The NM_001367484.1(GLIS1):​c.1320+21245G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,266 control chromosomes in the GnomAD database, including 2,023 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 0.15 (2023 hom., cov: 32)
• Consequence: GLIS1 NM_001367484.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367484.1. 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.1320+21245G>T		intron	N/A	NP_001354413.1
	GLIS1	NM_001390836.1		c.1344+18142G>T		intron	N/A	NP_001377765.1
	GLIS1	NM_001390837.1		c.1320+21245G>T		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.1320+21245G>T		intron	N/A	ENSP00000486112.1
	GLIS1	ENST00000312233.4	TSL:2	c.795+21245G>T		intron	N/A	ENSP00000309653.2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22250 AN: 152148 Hom.: 2023 Cov.: 32

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0981

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.146 AC: 22255 AN: 152266 Hom.: 2023 Cov.: 32 AF XY: 0.142 AC XY: 10596 AN XY: 74456

African (AFR) AF: 0.0473 AC: 1966 AN: 41556

American (AMR) AF: 0.0979 AC: 1498 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3472

East Asian (EAS) AF: 0.109 AC: 563 AN: 5174

South Asian (SAS) AF: 0.173 AC: 836 AN: 4828

European-Finnish (FIN) AF: 0.159 AC: 1689 AN: 10610

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14248 AN: 68004

Other (OTH) AF: 0.164 AC: 347 AN: 2112

Alfa AF: 0.168 Hom.: 3746

Bravo AF: 0.133

Asia WGS AF: 0.108 AC: 377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.38
PhyloP100		-0.052
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: rs10493174; hg19: chr1-54038536;