11-45882926-T-C

Position:

• chr11-45882926-T-C

Variant summary

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

The NM_021117.5(CRY2):​c.*2015T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 389,632 control chromosomes in the GnomAD database, including 142,917 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 0.85 (55507 hom., cov: 33)
  • Exomes 𝑓: 0.85 (87410 hom.)
• Consequence: CRY2 NM_021117.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY2	NM_021117.5	c.*2015T>C		3_prime_UTR_variant	12/12	ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3	c.*2015T>C		3_prime_UTR_variant	12/12		NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2	c.*2015T>C		3_prime_UTR_variant	12/12	1	NM_021117.5	ENSP00000484684.1
CRY2	ENST00000443527.6	c.*2015T>C		3_prime_UTR_variant	12/12	1		ENSP00000406751.2
CRY2	ENST00000616623.4	c.*2015T>C		3_prime_UTR_variant	12/12	1		ENSP00000478187.1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129094 AN: 152096 Hom.: 55469 Cov.: 33

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.859

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.851

GnomAD4 exome AF: 0.846 AC: 200807 AN: 237416 Hom.: 87410 Cov.: 0 AF XY: 0.848 AC XY: 102067 AN XY: 120346

Gnomad4 AFR exome AF: 0.784

Gnomad4 AMR exome AF: 0.872

Gnomad4 ASJ exome AF: 0.915

Gnomad4 EAS exome AF: 0.407

Gnomad4 SAS exome AF: 0.831

Gnomad4 FIN exome AF: 0.886

Gnomad4 NFE exome AF: 0.901

Gnomad4 OTH exome AF: 0.860

GnomAD4 genome AF: 0.849 AC: 129188 AN: 152216 Hom.: 55507 Cov.: 33 AF XY: 0.847 AC XY: 63044 AN XY: 74432

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.873

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.904

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.851

Alfa AF: 0.882 Hom.: 23583

Bravo AF: 0.842

Asia WGS AF: 0.745 AC: 2593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.42

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: rs6798; hg19: chr11-45904477;