chr11-45873085-C-G

Position:

• chr11-45873085-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.*2+852C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,168 control chromosomes in the GnomAD database, including 3,514 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 0.20 (3514 hom., cov: 32)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY2	NM_021117.5	c.*2+852C>G		intron_variant		ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3	c.*2+852C>G		intron_variant			NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2	c.*2+852C>G		intron_variant		1	NM_021117.5	ENSP00000484684.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31149 AN: 152050 Hom.: 3516 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.199

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.205 AC: 31152 AN: 152168 Hom.: 3514 Cov.: 32 AF XY: 0.204 AC XY: 15138 AN XY: 74378

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.198

Alfa AF: 0.0984 Hom.: 177

Bravo AF: 0.193

Asia WGS AF: 0.159 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.82

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: rs17787136; hg19: chr11-45894636;