11-45869957-A-G

Variant names:

• chr11-45869957-A-G
• rs4755345
• NM_021117.5:c.1195-96A>G

Variant summary

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

The NM_021117.5(CRY2):​c.1195-96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 1,516,554 control chromosomes in the GnomAD database, including 640,446 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 0.88 (59891 hom., cov: 34)
  • Exomes 𝑓: 0.92 (580555 hom.)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY2	NM_021117.5	c.1195-96A>G		intron_variant	Intron 7 of 11	ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3	c.1012-96A>G		intron_variant	Intron 7 of 11		NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2	c.1195-96A>G		intron_variant	Intron 7 of 11	1	NM_021117.5	ENSP00000484684.1

Frequencies

GnomAD3 genomes AF: 0.881 AC: 134075 AN: 152168 Hom.: 59852 Cov.: 34

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.882

GnomAD4 exome AF: 0.918 AC: 1252575 AN: 1364268 Hom.: 580555 Cov.: 31 AF XY: 0.917 AC XY: 614177 AN XY: 669672

Gnomad4 AFR exome AF: 0.806

Gnomad4 AMR exome AF: 0.875

Gnomad4 ASJ exome AF: 0.937

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.874

Gnomad4 FIN exome AF: 0.946

Gnomad4 NFE exome AF: 0.943

Gnomad4 OTH exome AF: 0.906

GnomAD4 genome AF: 0.881 AC: 134171 AN: 152286 Hom.: 59891 Cov.: 34 AF XY: 0.879 AC XY: 65463 AN XY: 74468

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.936

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.950

Gnomad4 NFE AF: 0.940

Gnomad4 OTH AF: 0.882

Alfa AF: 0.923 Hom.: 59202

Bravo AF: 0.870

Asia WGS AF: 0.758 AC: 2640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.66

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: rs4755345; hg19: chr11-45891508; COSMIC: COSV69888642; COSMIC: COSV69888642;