11-45856137-C-G

Variant names:

• chr11-45856137-C-G
• rs2292912
• NM_021117.5:c.324+47C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021117.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY2	NM_021117.5	MANE Select	c.324+47C>G		intron	N/A	NP_066940.3
	CRY2	NM_001127457.3		c.141+47C>G		intron	N/A	NP_001120929.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY2	ENST00000616080.2	TSL:1 MANE Select	c.324+47C>G		intron	N/A	ENSP00000484684.1
	CRY2	ENST00000443527.6	TSL:1	c.387+47C>G		intron	N/A	ENSP00000406751.2
	CRY2	ENST00000616623.4	TSL:1	c.387+47C>G		intron	N/A	ENSP00000478187.1

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

GnomAD2 exomes AF: 0.694 AC: 172407 AN: 248560 AF XY: 0.707

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 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

African (AFR) AF: 0.265 AC: 7921 AN: 29862

American (AMR) AF: 0.645 AC: 28360 AN: 43944

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 21467 AN: 25046

East Asian (EAS) AF: 0.358 AC: 13869 AN: 38698

South Asian (SAS) AF: 0.702 AC: 58224 AN: 82904

European-Finnish (FIN) AF: 0.742 AC: 39508 AN: 53240

Middle Eastern (MID) AF: 0.755 AC: 4038 AN: 5348

European-Non Finnish (NFE) AF: 0.800 AC: 782293 AN: 977982

Other (OTH) AF: 0.732 AC: 40462 AN: 55290

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

African (AFR) AF: 0.280 AC: 11612 AN: 41464

American (AMR) AF: 0.671 AC: 10259 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2962 AN: 3470

East Asian (EAS) AF: 0.370 AC: 1912 AN: 5170

South Asian (SAS) AF: 0.681 AC: 3276 AN: 4810

European-Finnish (FIN) AF: 0.764 AC: 8079 AN: 10576

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54088 AN: 67976

Other (OTH) AF: 0.659 AC: 1391 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.32
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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