chr1-47250368-TAA-T

Variant names:

• chr1-47250368-TAA-T
• rs75930208
• NM_001048166.1:c.*766_*767delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001048166.1(STIL):​c.*766_*767delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 173,964 control chromosomes in the GnomAD database, including 18,447 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (15821 hom., cov: 0)
  • Exomes 𝑓: 0.48 (2626 hom.)
• Consequence: STIL NM_001048166.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.61
• Publications: 1 publications found

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]

STIL Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• microcephaly 7, primary, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• holoprosencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-47250368-TAA-T is Benign according to our data. Variant chr1-47250368-TAA-T is described in ClinVar as Benign. ClinVar VariationId is 297544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001048166.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIL	NM_001048166.1	MANE Select	c.*766_*767delTT		3_prime_UTR	Exon 17 of 17	NP_001041631.1	Q15468-2
	STIL	NM_001282936.1		c.*766_*767delTT		3_prime_UTR	Exon 18 of 18	NP_001269865.1	Q15468-1
	STIL	NM_003035.2		c.*766_*767delTT		3_prime_UTR	Exon 17 of 17	NP_003026.2	Q15468-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIL	ENST00000371877.8	TSL:1 MANE Select	c.*766_*767delTT		3_prime_UTR	Exon 17 of 17	ENSP00000360944.3	Q15468-2
	STIL	ENST00000360380.7	TSL:1	c.*766_*767delTT		3_prime_UTR	Exon 18 of 18	ENSP00000353544.3	Q15468-1
	STIL	ENST00000936921.1		c.*766_*767delTT		3_prime_UTR	Exon 18 of 18	ENSP00000606980.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64521 AN: 151854 Hom.: 15808 Cov.: 0

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.477 AC: 10487 AN: 21990 Hom.: 2626 AF XY: 0.481 AC XY: 4851 AN XY: 10082

African (AFR) AF: 0.167 AC: 118 AN: 706

American (AMR) AF: 0.409 AC: 192 AN: 470

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 834 AN: 1316

East Asian (EAS) AF: 0.387 AC: 1884 AN: 4864

South Asian (SAS) AF: 0.474 AC: 92 AN: 194

European-Finnish (FIN) AF: 0.333 AC: 4 AN: 12

Middle Eastern (MID) AF: 0.522 AC: 70 AN: 134

European-Non Finnish (NFE) AF: 0.515 AC: 6454 AN: 12530

Other (OTH) AF: 0.476 AC: 839 AN: 1764

GnomAD4 genome AF: 0.425 AC: 64559 AN: 151974 Hom.: 15821 Cov.: 0 AF XY: 0.431 AC XY: 31994 AN XY: 74272

African (AFR) AF: 0.169 AC: 7027 AN: 41510

American (AMR) AF: 0.430 AC: 6566 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2276 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2315 AN: 5172

South Asian (SAS) AF: 0.551 AC: 2658 AN: 4822

European-Finnish (FIN) AF: 0.643 AC: 6767 AN: 10522

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.521 AC: 35396 AN: 67908

Other (OTH) AF: 0.463 AC: 975 AN: 2106

Alfa AF: 0.480 Hom.: 2330

Bravo AF: 0.396

Asia WGS AF: 0.492 AC: 1705 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary Microcephaly, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
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: rs75930208; hg19: chr1-47716040; COSMIC: COSV54547182; COSMIC: COSV54547182;