11-45882926-T-C

Variant names:

• chr11-45882926-T-C
• rs6798
• NM_021117.5:c.*2015T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021117.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY2	NM_021117.5	MANE Select	c.*2015T>C		3_prime_UTR	Exon 12 of 12	NP_066940.3
	CRY2	NM_001127457.3		c.*2015T>C		3_prime_UTR	Exon 12 of 12	NP_001120929.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY2	ENST00000616080.2	TSL:1 MANE Select	c.*2015T>C		3_prime_UTR	Exon 12 of 12	ENSP00000484684.1
	CRY2	ENST00000443527.6	TSL:1	c.*2015T>C		3_prime_UTR	Exon 12 of 12	ENSP00000406751.2
	CRY2	ENST00000616623.4	TSL:1	c.*2015T>C		3_prime_UTR	Exon 12 of 12	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

African (AFR) AF: 0.784 AC: 5476 AN: 6988

American (AMR) AF: 0.872 AC: 6219 AN: 7130

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 8219 AN: 8982

East Asian (EAS) AF: 0.407 AC: 9074 AN: 22282

South Asian (SAS) AF: 0.831 AC: 1742 AN: 2096

European-Finnish (FIN) AF: 0.886 AC: 17658 AN: 19926

Middle Eastern (MID) AF: 0.834 AC: 1044 AN: 1252

European-Non Finnish (NFE) AF: 0.901 AC: 137811 AN: 152984

Other (OTH) AF: 0.860 AC: 13564 AN: 15776

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

African (AFR) AF: 0.786 AC: 32630 AN: 41516

American (AMR) AF: 0.873 AC: 13358 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3177 AN: 3470

East Asian (EAS) AF: 0.458 AC: 2362 AN: 5158

South Asian (SAS) AF: 0.819 AC: 3952 AN: 4824

European-Finnish (FIN) AF: 0.904 AC: 9601 AN: 10622

Middle Eastern (MID) AF: 0.855 AC: 248 AN: 290

European-Non Finnish (NFE) AF: 0.900 AC: 61220 AN: 68012

Other (OTH) AF: 0.851 AC: 1800 AN: 2114

Alfa AF: 0.882 Hom.: 26944

Bravo AF: 0.842

Asia WGS AF: 0.745 AC: 2593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.42
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6798; hg19: chr11-45904477;