Genetic Variant NM_004075.5: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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004075.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CRY1	NM_004075.5	MANE Select	c.159-20836G>A	intron	N/A	NP_004066.1	A2I2P0
CRY1	NM_001413469.1		c.-431G>A	5_prime_UTR	Exon 2 of 14	NP_001400398.1
CRY1	NM_001413458.1		c.159-20836G>A	intron	N/A	NP_001400387.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CRY1	ENST00000008527.10	TSL:1 MANE Select	c.159-20836G>A	intron	N/A	ENSP00000008527.5	Q16526
CRY1	ENST00000864076.1		c.159-20836G>A	intron	N/A	ENSP00000534135.1
CRY1	ENST00000864077.1		c.159-20836G>A	intron	N/A	ENSP00000534136.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over