rs7123390

chr11-45869867-G-A

Variant summary

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

The NM_021117.5(CRY2):c.1194+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,548,998 control chromosomes in the GnomAD database, including 51,496 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 0.22 (3979 hom., cov: 33)
  • Exomes 𝑓: 0.26 (47517 hom.)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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 = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRY2	NM_021117.5	c.1194+50G>A		intron_variant		ENST00000616080.2
CRY2	NM_001127457.3	c.1011+50G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRY2	ENST00000616080.2	c.1194+50G>A		intron_variant		1	NM_021117.5	P2
CRY2	ENST00000443527.6	c.1257+50G>A		intron_variant		1		A2
CRY2	ENST00000616623.4	c.1257+50G>A		intron_variant		1		A2
CRY2	ENST00000417225.6	c.1011+50G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32953 AN: 152040 Hom.: 3982 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.214

GnomAD3 exomes AF: 0.216 AC: 42255 AN: 195384 Hom.: 5024 AF XY: 0.220 AC XY: 23194 AN XY: 105546

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.129

Gnomad SAS exome AF: 0.184

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.257 AC: 358728 AN: 1396840 Hom.: 47517 Cov.: 32 AF XY: 0.255 AC XY: 175383 AN XY: 687442

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.217 AC: 32952 AN: 152158 Hom.: 3979 Cov.: 33 AF XY: 0.215 AC XY: 15967 AN XY: 74372

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.213

Alfa AF: 0.255 Hom.: 5526

Bravo AF: 0.204

Asia WGS AF: 0.160 AC: 556 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	1.7
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: rs7123390; hg19: chr11-45891418; COSMIC: COSV69889074; COSMIC: COSV69889074;