Variant chr12-107001328-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004075.5(CRY1):c.636T>C(p.Gly212=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 1,611,886 control chromosomes in the GnomAD database, including 349,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.70 ( 38529 hom., cov: 32)

Exomes 𝑓: 0.65 ( 311123 hom. )

Consequence

CRY1
NM_004075.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.71

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 12-107001328-A-G is Benign according to our data. Variant chr12-107001328-A-G is described in ClinVar as [Benign]. Clinvar id is 3059240.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRY1	NM_004075.5 linkuse as main transcript	c.636T>C	p.Gly212=	synonymous_variant	5/13	ENST00000008527.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CRY1	ENST00000008527.10 linkuse as main transcript	c.636T>C	p.Gly212=	synonymous_variant	5/13	1	NM_004075.5	P1
CRY1	ENST00000546722.1 linkuse as main transcript	n.129T>C		non_coding_transcript_exon_variant	2/3	3
CRY1	ENST00000552790.5 linkuse as main transcript	n.1195T>C		non_coding_transcript_exon_variant	7/13	2

Frequencies

GnomAD3 genomes

AF:

0.702

AC:

106744

AN:

152000

Hom.:

38461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.826

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.763

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.968

Gnomad SAS

AF:

0.713

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.622

Gnomad OTH

AF:

0.683

GnomAD3 exomes

AF:

0.691

AC:

173239

AN:

250782

Hom.:

61605

AF XY:

0.683

AC XY:

92570

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.830

Gnomad AMR exome

AF:

0.809

Gnomad ASJ exome

AF:

0.556

Gnomad EAS exome

AF:

0.974

Gnomad SAS exome

AF:

0.715

Gnomad FIN exome

AF:

0.573

Gnomad NFE exome

AF:

0.619

Gnomad OTH exome

AF:

0.652

GnomAD4 exome

AF:

0.648

AC:

946094

AN:

1459766

Hom.:

311123

Cov.:

AF XY:

0.649

AC XY:

470993

AN XY:

726206

show subpopulations

Gnomad4 AFR exome

AF:

0.834

Gnomad4 AMR exome

AF:

0.802

Gnomad4 ASJ exome

AF:

0.549

Gnomad4 EAS exome

AF:

0.958

Gnomad4 SAS exome

AF:

0.714

Gnomad4 FIN exome

AF:

0.572

Gnomad4 NFE exome

AF:

0.625

Gnomad4 OTH exome

AF:

0.669

GnomAD4 genome

AF:

0.703

AC:

106880

AN:

152120

Hom.:

38529

Cov.:

AF XY:

0.705

AC XY:

52438

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.826

Gnomad4 AMR

AF:

0.764

Gnomad4 ASJ

AF:

0.551

Gnomad4 EAS

AF:

0.968

Gnomad4 SAS

AF:

0.714

Gnomad4 FIN

AF:

0.580

Gnomad4 NFE

AF:

0.622

Gnomad4 OTH

AF:

0.684

Alfa

AF:

0.638

Hom.:

68652

Bravo

AF:

0.722

Asia WGS

AF:

0.835

AC:

2901

AN:

3476

EpiCase

AF:

0.627

EpiControl

AF:

0.623

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CRY1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.41

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over