Genetic Variant CRY1:c.159-20836G>A (chr12-107043028-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004075.5(CRY1):c.159-20836G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,022 control chromosomes in the GnomAD database, including 37,472 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 0.69 ( 37463 hom., cov: 31)

Exomes 𝑓: 0.63 ( 9 hom. )

Consequence

CRY1
NM_004075.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.02

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY1	NM_004075.5 link	c.159-20836G>A		intron_variant	Intron 1 of 12	ENST00000008527.10	NP_004066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRY1	ENST00000008527.10 link	c.159-20836G>A		intron_variant	Intron 1 of 12	1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000552790.5 link	n.639G>A		non_coding_transcript_exon_variant	Exon 3 of 13	2

Frequencies

GnomAD3 genomes

AF:

0.694

AC:

105403

AN:

151860

Hom.:

37402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.798

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.759

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.968

Gnomad SAS

AF:

0.713

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.622

Gnomad OTH

AF:

0.677

GnomAD4 exome

AF:

0.630

AC:

AN:

Hom.:

Cov.:

AF XY:

0.553

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.694

AC:

105531

AN:

151976

Hom.:

37463

Cov.:

AF XY:

0.697

AC XY:

51801

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.798

AC:

33076

AN:

41444

American (AMR)

AF:

0.760

AC:

11607

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

1913

AN:

3470

East Asian (EAS)

AF:

0.968

AC:

5001

AN:

5168

South Asian (SAS)

AF:

0.714

AC:

3442

AN:

4818

European-Finnish (FIN)

AF:

0.582

AC:

6128

AN:

10522

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.622

AC:

42273

AN:

67970

Other (OTH)

AF:

0.678

AC:

1434

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1561

3122

4683

6244

7805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.563

Hom.:

1821

Bravo

AF:

0.713

Asia WGS

AF:

0.835

AC:

2902

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.38

(source)

DANN

Benign

0.88

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over