Variant 15-66386653-A-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.-12T>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 0.118 in 176,038 control chromosomes in the GnomAD database, including 1,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1164 hom., cov: 33)

Exomes 𝑓: 0.12 ( 168 hom. )

Consequence

TIPIN
NM_001398281.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.37

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=-0.84).

BP6

Variant 15-66386653-A-T is Benign according to our data. Variant chr15-66386653-A-T is described in ClinVar as [Benign]. Clinvar id is 561873.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
TIPIN	NM_001398281.1 linkuse as main transcript	c.-12T>A	5_prime_UTR_variant	1/8	NP_001385210.1
TIPIN	NM_001398283.1 linkuse as main transcript	c.-55T>A	5_prime_UTR_variant	1/8	NP_001385212.1
TIPIN	NM_001398285.1 linkuse as main transcript	c.-239T>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.-55T>A	5_prime_UTR_variant	1/8	5	ENSP00000457406
TIPIN	ENST00000568216.5 linkuse as main transcript	c.-12T>A	5_prime_UTR_variant	1/5	3	ENSP00000457172
TIPIN	ENST00000570251.1 linkuse as main transcript	c.-242T>A	5_prime_UTR_variant	1/5	3	ENSP00000458117
TIPIN	ENST00000561773.1 linkuse as main transcript	n.55T>A	non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17831

AN:

152112

Hom.:

1161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0679

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.0683

Gnomad SAS

AF:

0.0802

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.125

AC:

2970

AN:

23808

Hom.:

168

Cov.:

AF XY:

0.126

AC XY:

1386

AN XY:

11022

show subpopulations

Gnomad4 AFR exome

AF:

0.0534

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.0354

Gnomad4 FIN exome

AF:

0.0714

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.117

AC:

17856

AN:

152230

Hom.:

1164

Cov.:

AF XY:

0.115

AC XY:

8575

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0679

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.0685

Gnomad4 SAS

AF:

0.0802

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.134

Hom.:

174

Bravo

AF:

0.116

Asia WGS

AF:

0.0740

AC:

260

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

-0.84

CADD

Benign

2.3

DANN

Benign

0.55

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