rs1401417

Positions:

• chr11-45858559-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.325-172C>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 152,246 control chromosomes in the GnomAD database, including 3,126 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 (3126 hom., cov: 32)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY2	NM_021117.5	c.325-172C>G		intron_variant		ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3	c.142-172C>G		intron_variant			NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2	c.325-172C>G		intron_variant		1	NM_021117.5	ENSP00000484684	P2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29372 AN: 152128 Hom.: 3128 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.193 AC: 29374 AN: 152246 Hom.: 3126 Cov.: 32 AF XY: 0.192 AC XY: 14313 AN XY: 74430

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.188

Alfa AF: 0.220 Hom.: 477

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	-0.82
CADD	Benign	1.9
DANN	Benign	0.78

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: rs1401417; hg19: chr11-45880110;