rs10838527

Positions:

• chr11-45881643-A-G

Variant summary

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

The NM_021117.5(CRY2):​c.*732A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,214 control chromosomes in the GnomAD database, including 1,504 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 0.12 (1504 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRY2 NM_021117.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY2	NM_021117.5	c.*732A>G		3_prime_UTR_variant	12/12	ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3	c.*732A>G		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.*732A>G		3_prime_UTR_variant	12/12	1	NM_021117.5	ENSP00000484684	P2
CRY2	ENST00000443527.6	c.*732A>G		3_prime_UTR_variant	12/12	1		ENSP00000406751	A2
CRY2	ENST00000616623.4	c.*732A>G		3_prime_UTR_variant	12/12	1		ENSP00000478187	A2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18158 AN: 152096 Hom.: 1500 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.105

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 20 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.119 AC: 18174 AN: 152214 Hom.: 1504 Cov.: 33 AF XY: 0.119 AC XY: 8839 AN XY: 74432

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.0806

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0820

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0848 Hom.: 939

Bravo AF: 0.120

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.4
DANN	Benign	0.83

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: rs10838527; hg19: chr11-45903194;