20-37990856-C-T

Position:

• chr20-37990856-C-T

Variant summary

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

The NM_001303457.2(TTI1):​c.3086+5519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,066 control chromosomes in the GnomAD database, including 7,263 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 0.27 (7263 hom., cov: 32)
• Consequence: TTI1 NM_001303457.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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]

TTI1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTI1	NM_001303457.2	c.3086+5519G>A		intron_variant		ENST00000373447.8	NP_001290386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTI1	ENST00000373447.8	c.3086+5519G>A		intron_variant		1	NM_001303457.2	ENSP00000362546.3
TTI1	ENST00000373448.6	c.3086+5519G>A		intron_variant		1		ENSP00000362547.2
TTI1	ENST00000449821.1	c.3086+5519G>A		intron_variant		2		ENSP00000407270.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41575 AN: 151948 Hom.: 7242 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.274 AC: 41647 AN: 152066 Hom.: 7263 Cov.: 32 AF XY: 0.271 AC XY: 20180 AN XY: 74334

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.256

Alfa AF: 0.223 Hom.: 580

Bravo AF: 0.280

Asia WGS AF: 0.269 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.75

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: rs6022257; hg19: chr20-36619258;