rs3013777

Positions:

• chr1-53686948-T-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+50858A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,954 control chromosomes in the GnomAD database, including 21,205 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 0.51 (21205 hom., cov: 31)
• Consequence: GLIS1 NM_001367484.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS1	NM_001367484.1	c.259+50858A>G		intron_variant		ENST00000628545.2	NP_001354413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLIS1	ENST00000628545.2	c.259+50858A>G		intron_variant		5	NM_001367484.1	ENSP00000486112	P2
GLIS1	ENST00000312233.4	c.-267+46956A>G		intron_variant		2		ENSP00000309653	A2

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76900 AN: 151836 Hom.: 21196 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.506 AC: 76930 AN: 151954 Hom.: 21205 Cov.: 31 AF XY: 0.510 AC XY: 37890 AN XY: 74268

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.522

Alfa AF: 0.556 Hom.: 5959

Bravo AF: 0.485

Asia WGS AF: 0.469 AC: 1629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.59

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: rs3013777; hg19: chr1-54152621; COSMIC: COSV56545945; COSMIC: COSV56545945;