rs6022259

Positions:

• chr20-37991079-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001303457.2(TTI1):​c.3086+5296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,098 control chromosomes in the GnomAD database, including 7,834 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 0.28 (7834 hom., cov: 33)
• Consequence: TTI1 NM_001303457.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

Genes affected

TTI1 (HGNC:29029): (TELO2 interacting protein 1) Involved in regulation of TOR signaling. Located in cytoplasm. Part of TORC1 complex and TORC2 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTI1	NM_001303457.2	c.3086+5296G>A		intron_variant		ENST00000373447.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTI1	ENST00000373447.8	c.3086+5296G>A		intron_variant		1	NM_001303457.2	P1
TTI1	ENST00000373448.6	c.3086+5296G>A		intron_variant		1		P1
TTI1	ENST00000449821.1	c.3086+5296G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42797 AN: 151978 Hom.: 7812 Cov.: 33

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.282 AC: 42879 AN: 152098 Hom.: 7834 Cov.: 33 AF XY: 0.280 AC XY: 20795 AN XY: 74354

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.265

Alfa AF: 0.196 Hom.: 5415

Bravo AF: 0.289

Asia WGS AF: 0.287 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.79

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: rs6022259; hg19: chr20-36619481;