chr11-45856910-G-A

Position:

• chr11-45856910-G-A

Variant summary

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

The NM_021117.5(CRY2):​c.324+820G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 151,940 control chromosomes in the GnomAD database, including 359 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 0.057 (359 hom., cov: 32)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY2	NM_021117.5	c.324+820G>A		intron_variant		ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3	c.141+820G>A		intron_variant			NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2	c.324+820G>A		intron_variant		1	NM_021117.5	ENSP00000484684	P2

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8738 AN: 151844 Hom.: 359 Cov.: 32

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.0519

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

GnomAD4 genome AF: 0.0575 AC: 8733 AN: 151940 Hom.: 359 Cov.: 32 AF XY: 0.0584 AC XY: 4334 AN XY: 74226

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.0576

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0809

Gnomad4 OTH AF: 0.0513

Alfa AF: 0.0728 Hom.: 583

Bravo AF: 0.0507

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.0
DANN	Benign	0.49

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: rs11038695; hg19: chr11-45878461;