1-47250820-A-G

Variant names:

• chr1-47250820-A-G
• rs11211488
• NM_001048166.1:c.*316T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001048166.1(STIL):​c.*316T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 242,694 control chromosomes in the GnomAD database, including 2,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.093 (2166 hom., cov: 33)
  • Exomes 𝑓: 0.015 (179 hom.)
• Consequence: STIL NM_001048166.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.451

Genes affected

STIL (HGNC:10879): (STIL centriolar assembly protein) This gene encodes a cytoplasmic protein implicated in regulation of the mitotic spindle checkpoint, a regulatory pathway that monitors chromosome segregation during cell division to ensure the proper distribution of chromosomes to daughter cells. The protein is phosphorylated in mitosis and in response to activation of the spindle checkpoint, and disappears when cells transition to G1 phase. It interacts with a mitotic regulator, and its expression is required to efficiently activate the spindle checkpoint. It is proposed to regulate Cdc2 kinase activity during spindle checkpoint arrest. Chromosomal deletions that fuse this gene and the adjacent locus commonly occur in T cell leukemias, and are thought to arise through illegitimate V-(D)-J recombination events. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-47250820-A-G is Benign according to our data. Variant chr1-47250820-A-G is described in ClinVar as [Benign]. Clinvar id is 297548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIL	NM_001048166.1	c.*316T>C		3_prime_UTR_variant	Exon 17 of 17	ENST00000371877.8	NP_001041631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIL	ENST00000371877	c.*316T>C		3_prime_UTR_variant	Exon 17 of 17	1	NM_001048166.1	ENSP00000360944.3

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14122 AN: 151532 Hom.: 2163 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.0604

GnomAD4 exome AF: 0.0149 AC: 1359 AN: 91046 Hom.: 179 Cov.: 0 AF XY: 0.0135 AC XY: 602 AN XY: 44686

Gnomad4 AFR exome AF: 0.302

Gnomad4 AMR exome AF: 0.0284

Gnomad4 ASJ exome AF: 0.000935

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000962

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00136

Gnomad4 OTH exome AF: 0.0283

GnomAD4 genome AF: 0.0933 AC: 14154 AN: 151648 Hom.: 2166 Cov.: 33 AF XY: 0.0907 AC XY: 6718 AN XY: 74108

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00150

Gnomad4 OTH AF: 0.0598

Alfa AF: 0.0737 Hom.: 164

Bravo AF: 0.106

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microcephaly 7, primary, autosomal recessive Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.5
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11211488; hg19: chr1-47716492;