chr1-53690951-A-C

Position:

• chr1-53690951-A-C

Variant summary

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

The NM_001367484.1(GLIS1):​c.259+46855T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,142 control chromosomes in the GnomAD database, including 3,992 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 (3992 hom., cov: 32)
• Consequence: GLIS1 NM_001367484.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLIS1	NM_001367484.1	c.259+46855T>G		intron_variant		ENST00000628545.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLIS1	ENST00000628545.2	c.259+46855T>G		intron_variant		5	NM_001367484.1	P2
GLIS1	ENST00000312233.4	c.-267+42953T>G		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34372 AN: 152024 Hom.: 3988 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.226 AC: 34398 AN: 152142 Hom.: 3992 Cov.: 32 AF XY: 0.221 AC XY: 16444 AN XY: 74388

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.236

Alfa AF: 0.193 Hom.: 1511

Bravo AF: 0.235

Asia WGS AF: 0.198 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.55

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: rs12082358; hg19: chr1-54156624;