Variant 12-106992962-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004075.5(CRY1):c.1657+3A>C variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00438 in 1,614,074 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association,risk factor (no stars).

Frequency

Genomes: 𝑓 0.0037 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 36 hom. )

Consequence

CRY1
NM_004075.5 splice_donor_region, intron

Scores

Splicing: ADA: 0.9984

Clinical Significance

association; risk factor no assertion criteria provided O:2

Conservation

PhyloP100: 4.18

Variant links:

Genes affected

CRY1 (HGNC:2384): (cryptochrome circadian regulator 1) This gene encodes a flavin adenine dinucleotide-binding protein that is a key component of the circadian core oscillator complex, which regulates the circadian clock. This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL. Polymorphisms in this gene have been associated with altered sleep patterns. The encoded protein is widely conserved across plants and animals. Loss of the related gene in mouse results in a shortened circadian cycle in complete darkness. [provided by RefSeq, Jan 2014]

CRY1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 569 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY1	NM_004075.5 linkuse as main transcript	c.1657+3A>C		splice_donor_region_variant, intron_variant		ENST00000008527.10	NP_004066.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
CRY1	ENST00000008527.10 linkuse as main transcript	c.1657+3A>C	splice_donor_region_variant, intron_variant		1	NM_004075.5	ENSP00000008527	P1
CRY1	ENST00000549356.1 linkuse as main transcript	c.217+3A>C	splice_donor_region_variant, intron_variant		3		ENSP00000447738
CRY1	ENST00000552790.5 linkuse as main transcript	n.2239A>C	non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes

AF:

0.00375

AC:

570

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.0374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00456

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00461

AC:

1158

AN:

251380

Hom.:

AF XY:

0.00470

AC XY:

638

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00413

Gnomad ASJ exome

AF:

0.0332

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00206

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00495

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00445

AC:

6502

AN:

1461756

Hom.:

Cov.:

AF XY:

0.00457

AC XY:

3321

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00425

Gnomad4 ASJ exome

AF:

0.0308

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00185

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.00437

Gnomad4 OTH exome

AF:

0.00646

GnomAD4 genome

AF:

0.00374

AC:

569

AN:

152318

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

289

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00568

Gnomad4 ASJ

AF:

0.0374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00456

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00517

Hom.:

Bravo

AF:

0.00419

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00562

EpiControl

AF:

0.00616

ClinVar

Significance: association; risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Delayed sleep phase syndrome, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 25, 2017

- -

Sleep-wake schedule disorder, delayed phase type;C1263846:Attention deficit hyperactivity disorder

Other:1

association, no assertion criteria provided

literature only

Yale Center for Mendelian Genomics, Yale University

Jul 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.94

SpliceAI score (max)

0.93

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.93

Position offset: 3

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