11-45851540-A-C

Position:

• chr11-45851540-A-C

Variant summary

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

The NM_021117.5(CRY2):​c.215+3835A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,090 control chromosomes in the GnomAD database, including 14,563 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 0.40 (14563 hom., cov: 32)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY2	NM_021117.5	c.215+3835A>C		intron_variant		ENST00000616080.2	NP_066940.3
CRY2	NM_001127457.3	c.32+4259A>C		intron_variant			NP_001120929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY2	ENST00000616080.2	c.215+3835A>C		intron_variant		1	NM_021117.5	ENSP00000484684	P2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60547 AN: 151972 Hom.: 14551 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.398 AC: 60579 AN: 152090 Hom.: 14563 Cov.: 32 AF XY: 0.400 AC XY: 29735 AN XY: 74316

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.437

Alfa AF: 0.505 Hom.: 25354

Bravo AF: 0.387

Asia WGS AF: 0.396 AC: 1381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.59

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: rs11605924; hg19: chr11-45873091;