rs1040404

Variant names:

• chr1-168190652-G-A
• rs1040404
• NM_152902.5:c.385-717G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-168190652-G-A
• chr1-168190652-G-C
• chr1-168190652-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TIPRL	NM_152902.5	c.385-717G>A		intron_variant	Intron 3 of 6	ENST00000367833.7	NP_690866.1
TIPRL	NM_001031800.3	c.385-717G>A		intron_variant	Intron 3 of 4		NP_001026970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIPRL	ENST00000367833.7	c.385-717G>A		intron_variant	Intron 3 of 6	1	NM_152902.5	ENSP00000356807.2
TIPRL	ENST00000367830.3	c.385-717G>A		intron_variant	Intron 3 of 4	1		ENSP00000356804.3

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

African (AFR) AF: 0.786 AC: 32603 AN: 41498

American (AMR) AF: 0.565 AC: 8619 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1341 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2123 AN: 5166

South Asian (SAS) AF: 0.239 AC: 1151 AN: 4818

European-Finnish (FIN) AF: 0.401 AC: 4238 AN: 10568

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21231 AN: 67960

Other (OTH) AF: 0.457 AC: 966 AN: 2112

Alfa AF: 0.433 Hom.: 13974

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
PhyloP100		0.17
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: rs1040404; hg19: chr1-168159890;