rs11038689

Variant names:

• chr11-45852713-A-G
• rs11038689
• NM_021117.5:c.216-3269A>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.216-3269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,230 control chromosomes in the GnomAD database, including 3,142 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 0.19 (3142 hom., cov: 33)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886
• Publications: 16 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY2	NM_021117.5	c.216-3269A>G		intron_variant	Intron 1 of 11	ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3	c.33-3269A>G		intron_variant	Intron 1 of 11		NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2	c.216-3269A>G		intron_variant	Intron 1 of 11	1	NM_021117.5	ENSP00000484684.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29436 AN: 152112 Hom.: 3144 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.193 AC: 29438 AN: 152230 Hom.: 3142 Cov.: 33 AF XY: 0.193 AC XY: 14345 AN XY: 74422

African (AFR) AF: 0.127 AC: 5262 AN: 41556

American (AMR) AF: 0.139 AC: 2124 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3470

East Asian (EAS) AF: 0.128 AC: 662 AN: 5184

South Asian (SAS) AF: 0.171 AC: 826 AN: 4824

European-Finnish (FIN) AF: 0.274 AC: 2906 AN: 10590

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16266 AN: 67988

Other (OTH) AF: 0.188 AC: 397 AN: 2114

Alfa AF: 0.218 Hom.: 10467

Bravo AF: 0.181

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		0.89
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: rs11038689; hg19: chr11-45874264;