Variant 15-66386717-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001398281.1(TIPIN):c.-76G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.058 in 186,688 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.056 ( 346 hom., cov: 33)

Exomes 𝑓: 0.065 ( 89 hom. )

Consequence

TIPIN
NM_001398281.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.451

Variant links:

Genes affected

TIPIN (HGNC:30750): (TIMELESS interacting protein) The protein encoded by this gene is part of the replisome complex, a group of proteins that support DNA replication. It binds TIM, which is involved in circadian rhythm regulation, and aids in protecting cells against DNA damage and stress. Two pseudogenes and two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

TIPIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-66386717-C-T is Benign according to our data. Variant chr15-66386717-C-T is described in ClinVar as [Benign]. Clinvar id is 561875.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
TIPIN	NM_001398281.1 linkuse as main transcript	c.-76G>A	5_prime_UTR_variant	1/8	NP_001385210.1
TIPIN	NM_001398283.1 linkuse as main transcript	c.-119G>A	5_prime_UTR_variant	1/8	NP_001385212.1
TIPIN	NM_001398285.1 linkuse as main transcript	c.-303G>A	5_prime_UTR_variant	1/7	NP_001385214.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein
TIPIN	ENST00000562124.5 linkuse as main transcript	c.-119G>A	5_prime_UTR_variant	1/8	5	ENSP00000457406
TIPIN	ENST00000570251.1 linkuse as main transcript	c.-306G>A	5_prime_UTR_variant	1/5	3	ENSP00000458117
TIPIN	ENST00000568216.5 linkuse as main transcript		upstream_gene_variant		3	ENSP00000457172
TIPIN	ENST00000561773.1 linkuse as main transcript		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0564

AC:

8588

AN:

152210

Hom.:

345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0235

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0451

Gnomad ASJ

AF:

0.0930

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0285

Gnomad FIN

AF:

0.0801

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0787

Gnomad OTH

AF:

0.0659

GnomAD4 exome

AF:

0.0653

AC:

2242

AN:

34360

Hom.:

Cov.:

AF XY:

0.0672

AC XY:

1077

AN XY:

16016

show subpopulations

Gnomad4 AFR exome

AF:

0.0163

Gnomad4 AMR exome

AF:

0.0414

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0847

Gnomad4 OTH exome

AF:

0.0769

GnomAD4 genome

AF:

0.0564

AC:

8591

AN:

152328

Hom.:

346

Cov.:

AF XY:

0.0561

AC XY:

4180

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0235

Gnomad4 AMR

AF:

0.0450

Gnomad4 ASJ

AF:

0.0930

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0292

Gnomad4 FIN

AF:

0.0801

Gnomad4 NFE

AF:

0.0787

Gnomad4 OTH

AF:

0.0662

Alfa

AF:

0.0273

Hom.:

Bravo

AF:

0.0523

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.5

DANN

Benign

0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over