11-45856137-C-G

Position:

• chr11-45856137-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021117.5(CRY2):​c.324+47C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,464,378 control chromosomes in the GnomAD database, including 420,308 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 0.62 (33459 hom., cov: 32)
  • Exomes 𝑓: 0.76 (386849 hom.)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY2	NM_021117.5	c.324+47C>G		intron_variant		ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3	c.141+47C>G		intron_variant			NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2	c.324+47C>G		intron_variant		1	NM_021117.5	ENSP00000484684	P2

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94546 AN: 151946 Hom.: 33453 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.656

GnomAD3 exomes AF: 0.694 AC: 172407 AN: 248560 Hom.: 63029 AF XY: 0.707 AC XY: 94999 AN XY: 134444

Gnomad AFR exome AF: 0.272

Gnomad AMR exome AF: 0.643

Gnomad ASJ exome AF: 0.853

Gnomad EAS exome AF: 0.377

Gnomad SAS exome AF: 0.696

Gnomad FIN exome AF: 0.748

Gnomad NFE exome AF: 0.793

Gnomad OTH exome AF: 0.738

GnomAD4 exome AF: 0.759 AC: 996142 AN: 1312314 Hom.: 386849 Cov.: 18 AF XY: 0.760 AC XY: 501971 AN XY: 660698

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.645

Gnomad4 ASJ exome AF: 0.857

Gnomad4 EAS exome AF: 0.358

Gnomad4 SAS exome AF: 0.702

Gnomad4 FIN exome AF: 0.742

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 0.732

GnomAD4 genome AF: 0.622 AC: 94576 AN: 152064 Hom.: 33459 Cov.: 32 AF XY: 0.622 AC XY: 46207 AN XY: 74330

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.659

Alfa AF: 0.700 Hom.: 5118

Bravo AF: 0.599

Asia WGS AF: 0.561 AC: 1953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.32

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

Other links and lift over

dbSNP: rs2292912; hg19: chr11-45877688; COSMIC: COSV69889414; COSMIC: COSV69889414;