rs6022419

Positions:

• chr20-38021663-A-G
• chr20-38021663-A-T

Variant summary

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

The NM_001303457.2(TTI1):​c.-41-7806T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,022 control chromosomes in the GnomAD database, including 13,508 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 0.41 (13508 hom., cov: 31)
• Consequence: TTI1 NM_001303457.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTI1	NM_001303457.2	c.-41-7806T>C		intron_variant		ENST00000373447.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTI1	ENST00000373447.8	c.-41-7806T>C		intron_variant		1	NM_001303457.2	P1
TTI1	ENST00000373448.6	c.-181-2519T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61773 AN: 151902 Hom.: 13480 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.407 AC: 61858 AN: 152022 Hom.: 13508 Cov.: 31 AF XY: 0.404 AC XY: 30017 AN XY: 74310

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.374

Alfa AF: 0.346 Hom.: 12380

Bravo AF: 0.415

Asia WGS AF: 0.358 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.025
DANN	Benign	0.45

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: rs6022419; hg19: chr20-36650065;