dbSNP rs7123390: CRY2:c.1194+50G>A (chr11-45869867-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021117.5(CRY2):c.1194+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,548,998 control chromosomes in the GnomAD database, including 51,496 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 0.22 ( 3979 hom., cov: 33)

Exomes 𝑓: 0.26 ( 47517 hom. )

Consequence

CRY2
NM_021117.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0780

Publications

21 publications found

Variant links:

Genes affected

CRY2 (HGNC:2385): (cryptochrome circadian regulator 2) 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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]

CRY2 links:

Genome browser will be placed here

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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY2	NM_021117.5 link	c.1194+50G>A		intron_variant	Intron 7 of 11	ENST00000616080.2	NP_066940.3	Q49AN0-1A0A0D2X7Z3A2I2P1
CRY2	NM_001127457.3 link	c.1011+50G>A		intron_variant	Intron 7 of 11		NP_001120929.1	Q49AN0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2 link	c.1194+50G>A		intron_variant	Intron 7 of 11	1	NM_021117.5	ENSP00000484684.1		Q49AN0-1

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32953

AN:

152040

Hom.:

3982

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.214

GnomAD2 exomes

AF:

0.216

AC:

42255

AN:

195384

AF XY:

0.220

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.129

Gnomad FIN exome

AF:

0.283

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.257

AC:

358728

AN:

1396840

Hom.:

47517

Cov.:

AF XY:

0.255

AC XY:

175383

AN XY:

687442

show subpopulations

African (AFR)

AF:

0.127

AC:

4056

AN:

32000

American (AMR)

AF:

0.123

AC:

4779

AN:

38786

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

6048

AN:

22116

East Asian (EAS)

AF:

0.144

AC:

5634

AN:

39056

South Asian (SAS)

AF:

0.185

AC:

14398

AN:

77678

European-Finnish (FIN)

AF:

0.275

AC:

12687

AN:

46156

Middle Eastern (MID)

AF:

0.213

AC:

1099

AN:

5154

European-Non Finnish (NFE)

AF:

0.274

AC:

295997

AN:

1078388

Other (OTH)

AF:

0.244

AC:

14030

AN:

57506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

15361

30722

46084

61445

76806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10000

20000

30000

40000

50000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.217

AC:

32952

AN:

152158

Hom.:

3979

Cov.:

AF XY:

0.215

AC XY:

15967

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.132

AC:

5492

AN:

41538

American (AMR)

AF:

0.167

AC:

2549

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

933

AN:

3464

East Asian (EAS)

AF:

0.128

AC:

662

AN:

5164

South Asian (SAS)

AF:

0.177

AC:

855

AN:

4826

European-Finnish (FIN)

AF:

0.287

AC:

3034

AN:

10588

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18652

AN:

67964

Other (OTH)

AF:

0.213

AC:

450

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1330

2660

3990

5320

6650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.251

Hom.:

7577

Bravo

AF:

0.204

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.7

(source)

DANN

Benign

0.65

PhyloP100

-0.078

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over