rs1040404

chr1-168190652-G-A

Variant summary

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

The NM_152902.5(TIPRL):c.385-717G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,058 control chromosomes in the GnomAD database, including 20,630 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 0.48 (20630 hom., cov: 32)
• Consequence: TIPRL NM_152902.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

Genes affected

TIPRL (HGNC:30231): (TOR signaling pathway regulator) TIPRL is an inhibitory regulator of protein phosphatase-2A (PP2A) (see PPP2CA; MIM 176915), PP4 (see PPP4C; MIM 602035), and PP6 (see PPP6C; MIM 612725) (McConnell et al., 2007 [PubMed 17384681]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIPRL	NM_152902.5	c.385-717G>A		intron_variant		ENST00000367833.7
TIPRL	NM_001031800.3	c.385-717G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIPRL	ENST00000367833.7	c.385-717G>A		intron_variant		1	NM_152902.5	P1
TIPRL	ENST00000367830.3	c.385-717G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72623 AN: 151940 Hom.: 20577 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.478 AC: 72729 AN: 152058 Hom.: 20630 Cov.: 32 AF XY: 0.479 AC XY: 35621 AN XY: 74338

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.457

Alfa AF: 0.363 Hom.: 5973

Bravo AF: 0.511

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.71

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: rs1040404; hg19: chr1-168159890;