Variant rs7123390 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CRY2	NM_021117.5 linkuse as main transcript	c.1194+50G>A		intron_variant		ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3 linkuse as main transcript	c.1011+50G>A		intron_variant			NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2 linkuse as main transcript	c.1194+50G>A	intron_variant	1	NM_021117.5	ENSP00000484684	P2	Q49AN0-1
CRY2	ENST00000443527.6 linkuse as main transcript	c.1257+50G>A	intron_variant	1		ENSP00000406751	A2
CRY2	ENST00000616623.4 linkuse as main transcript	c.1257+50G>A	intron_variant	1		ENSP00000478187	A2
CRY2	ENST00000417225.6 linkuse as main transcript	c.1011+50G>A	intron_variant	2		ENSP00000397419		Q49AN0-2

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

GnomAD3 exomes

AF:

0.216

AC:

42255

AN:

195384

Hom.:

5024

AF XY:

0.220

AC XY:

23194

AN XY:

105546

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 SAS exome

AF:

0.184

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

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.275

Gnomad4 NFE exome

AF:

0.274

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.217

AC:

32952

AN:

152158

Hom.:

3979

Cov.:

AF XY:

0.215

AC XY:

15967

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.128

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.287

Gnomad4 NFE

AF:

0.274

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.255

Hom.:

5526

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

DANN

Benign

0.65

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over