Variant rs774026 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003920.5(TIMELESS):c.1578+22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,558,304 control chromosomes in the GnomAD database, including 163,925 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 ( 14441 hom., cov: 32)

Exomes 𝑓: 0.45 ( 149484 hom. )

Consequence

TIMELESS
NM_003920.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.659

Variant links:

Genes affected

TIMELESS (HGNC:11813): (timeless circadian regulator) The protein encoded by this gene is highly conserved and is involved in cell survival after damage or stress, increase in DNA polymerase epsilon activity, maintenance of telomere length, and epithelial cell morphogenesis. The encoded protein also plays a role in the circadian rhythm autoregulatory loop, interacting with the PERIOD genes (PER1, PER2, and PER3) and others to downregulate activation of PER1 by CLOCK/ARNTL. Changes in this gene or its expression may promote prostate cancer, lung cancer, breast cancer, and mental disorders. [provided by RefSeq, Feb 2014]

TIMELESS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TIMELESS	NM_003920.5 link	c.1578+22T>C	intron_variant	ENST00000553532.6	NP_003911.2	Q9UNS1-1
TIMELESS	NM_001330295.2 link	c.1575+22T>C	intron_variant		NP_001317224.1	Q9UNS1-2
TIMELESS	NR_138471.2 link	n.1756+22T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMELESS	ENST00000553532.6 link	c.1578+22T>C		intron_variant		1	NM_003920.5	ENSP00000450607.1		Q9UNS1-1
TIMELESS	ENST00000229201.4 link	c.1575+22T>C		intron_variant		5		ENSP00000229201.4		Q9UNS1-2

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62880

AN:

151854

Hom.:

14437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.530

Gnomad EAS

AF:

0.728

Gnomad SAS

AF:

0.500

Gnomad FIN

AF:

0.406

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.488

GnomAD3 exomes

AF:

0.499

AC:

108414

AN:

217318

Hom.:

29159

AF XY:

0.496

AC XY:

58186

AN XY:

117284

show subpopulations

Gnomad AFR exome

AF:

0.231

Gnomad AMR exome

AF:

0.711

Gnomad ASJ exome

AF:

0.519

Gnomad EAS exome

AF:

0.742

Gnomad SAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.417

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.497

GnomAD4 exome

AF:

0.454

AC:

639025

AN:

1406334

Hom.:

149484

Cov.:

AF XY:

0.456

AC XY:

315998

AN XY:

693694

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.695

Gnomad4 ASJ exome

AF:

0.525

Gnomad4 EAS exome

AF:

0.671

Gnomad4 SAS exome

AF:

0.497

Gnomad4 FIN exome

AF:

0.423

Gnomad4 NFE exome

AF:

0.441

Gnomad4 OTH exome

AF:

0.469

GnomAD4 genome

AF:

0.414

AC:

62894

AN:

151970

Hom.:

14441

Cov.:

AF XY:

0.418

AC XY:

31005

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.239

Gnomad4 AMR

AF:

0.576

Gnomad4 ASJ

AF:

0.530

Gnomad4 EAS

AF:

0.727

Gnomad4 SAS

AF:

0.499

Gnomad4 FIN

AF:

0.406

Gnomad4 NFE

AF:

0.448

Gnomad4 OTH

AF:

0.483

Alfa

AF:

0.450

Hom.:

2999

Bravo

AF:

0.429

Asia WGS

AF:

0.557

AC:

1938

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over