NM_021117.5:c.325-1290A>G

Variant names:

• chr11-45857441-A-G
• rs7945565
• NM_021117.5:c.325-1290A>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.325-1290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,038 control chromosomes in the GnomAD database, including 14,546 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 0.40 (14546 hom., cov: 32)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 14 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 = 0.516 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.325-1290A>G		intron	N/A	NP_066940.3	A2I2P1
	CRY2	NM_001127457.3		c.142-1290A>G		intron	N/A	NP_001120929.1	Q49AN0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY2	ENST00000616080.2	TSL:1 MANE Select	c.325-1290A>G		intron	N/A	ENSP00000484684.1	Q49AN0-1
	CRY2	ENST00000443527.6	TSL:1	c.388-1290A>G		intron	N/A	ENSP00000406751.2	A0A0D2X7Z3
	CRY2	ENST00000616623.4	TSL:1	c.388-1290A>G		intron	N/A	ENSP00000478187.1	A0A0D2X7Z3

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60402 AN: 151920 Hom.: 14537 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.397 AC: 60423 AN: 152038 Hom.: 14546 Cov.: 32 AF XY: 0.399 AC XY: 29662 AN XY: 74312

African (AFR) AF: 0.124 AC: 5136 AN: 41488

American (AMR) AF: 0.502 AC: 7649 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1993 AN: 3472

East Asian (EAS) AF: 0.243 AC: 1258 AN: 5176

South Asian (SAS) AF: 0.506 AC: 2441 AN: 4828

European-Finnish (FIN) AF: 0.477 AC: 5030 AN: 10552

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35356 AN: 67954

Other (OTH) AF: 0.437 AC: 922 AN: 2112

Alfa AF: 0.472 Hom.: 34194

Bravo AF: 0.386

Asia WGS AF: 0.400 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.76
PhyloP100		0.21
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: rs7945565; hg19: chr11-45878992;