rs10838524

Variant names:

• chr11-45848626-A-G
• rs10838524
• NM_021117.5:c.215+921A>G

Variant summary

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

The NM_021117.5(CRY2):​c.215+921A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,100 control chromosomes in the GnomAD database, including 16,416 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 0.42 (16416 hom., cov: 32)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY2	NM_021117.5	c.215+921A>G		intron_variant	Intron 1 of 11	ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3	c.32+1345A>G		intron_variant	Intron 1 of 11		NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2	c.215+921A>G		intron_variant	Intron 1 of 11	1	NM_021117.5	ENSP00000484684.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64087 AN: 151982 Hom.: 16407 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.458

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.421 AC: 64104 AN: 152100 Hom.: 16416 Cov.: 32 AF XY: 0.422 AC XY: 31380 AN XY: 74348

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.462

Alfa AF: 0.539 Hom.: 24532

Bravo AF: 0.410

Asia WGS AF: 0.409 AC: 1424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.24

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: rs10838524; hg19: chr11-45870177;