chr11-45848626-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 55 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 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.215+921A>G		intron	N/A	NP_066940.3
	CRY2	NM_001127457.3		c.32+1345A>G		intron	N/A	NP_001120929.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY2	ENST00000616080.2	TSL:1 MANE Select	c.215+921A>G		intron	N/A	ENSP00000484684.1
	CRY2	ENST00000443527.6	TSL:1	c.278+921A>G		intron	N/A	ENSP00000406751.2
	CRY2	ENST00000616623.4	TSL:1	c.278+921A>G		intron	N/A	ENSP00000478187.1

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

African (AFR) AF: 0.130 AC: 5395 AN: 41512

American (AMR) AF: 0.529 AC: 8089 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2222 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1254 AN: 5178

South Asian (SAS) AF: 0.514 AC: 2475 AN: 4816

European-Finnish (FIN) AF: 0.491 AC: 5186 AN: 10568

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37803 AN: 67960

Other (OTH) AF: 0.462 AC: 976 AN: 2114

Alfa AF: 0.524 Hom.: 34593

Bravo AF: 0.410

Asia WGS AF: 0.409 AC: 1424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.24
PhyloP100		0.16
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: rs10838524; hg19: chr11-45870177;