rs1401419

Variant names:

• chr11-45858188-T-C
• rs1401419
• NM_021117.5:c.325-543T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021117.5(CRY2):​c.325-543T>C 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 152,240 control chromosomes in the GnomAD database, including 14,568 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 (14550 hom., cov: 32)
  • Exomes 𝑓: 0.52 (18 hom.)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY2	NM_021117.5	c.325-543T>C		intron_variant	Intron 2 of 11	ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3	c.142-543T>C		intron_variant	Intron 2 of 11		NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2	c.325-543T>C		intron_variant	Intron 2 of 11	1	NM_021117.5	ENSP00000484684.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60400 AN: 151998 Hom.: 14541 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.524 AC: 65 AN: 124 Hom.: 18 AF XY: 0.500 AC XY: 36 AN XY: 72

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.397 AC: 60422 AN: 152116 Hom.: 14550 Cov.: 32 AF XY: 0.399 AC XY: 29662 AN XY: 74346

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.437

Alfa AF: 0.450 Hom.: 2112

Bravo AF: 0.386

Asia WGS AF: 0.393 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.65

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: rs1401419; hg19: chr11-45879739;