chr11-45858559-C-G

Variant names:

• chr11-45858559-C-G
• rs1401417
• NM_021117.5:c.325-172C>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.325-172C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,246 control chromosomes in the GnomAD database, including 3,126 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 0.19 (3126 hom., cov: 32)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 25 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY2	NM_021117.5	MANE Select	c.325-172C>G		intron	N/A	NP_066940.3	A2I2P1
	CRY2	NM_001127457.3		c.142-172C>G		intron	N/A	NP_001120929.1	Q49AN0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY2	ENST00000616080.2	TSL:1 MANE Select	c.325-172C>G		intron	N/A	ENSP00000484684.1	Q49AN0-1
	CRY2	ENST00000443527.6	TSL:1	c.388-172C>G		intron	N/A	ENSP00000406751.2	A0A0D2X7Z3
	CRY2	ENST00000616623.4	TSL:1	c.388-172C>G		intron	N/A	ENSP00000478187.1	A0A0D2X7Z3

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29372 AN: 152128 Hom.: 3128 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.193 AC: 29374 AN: 152246 Hom.: 3126 Cov.: 32 AF XY: 0.192 AC XY: 14313 AN XY: 74430

African (AFR) AF: 0.126 AC: 5248 AN: 41538

American (AMR) AF: 0.139 AC: 2131 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3470

East Asian (EAS) AF: 0.128 AC: 665 AN: 5190

South Asian (SAS) AF: 0.170 AC: 822 AN: 4824

European-Finnish (FIN) AF: 0.273 AC: 2891 AN: 10586

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16225 AN: 68016

Other (OTH) AF: 0.188 AC: 398 AN: 2112

Alfa AF: 0.220 Hom.: 477

Bravo AF: 0.181

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.78
PhyloP100		-0.41
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: rs1401417; hg19: chr11-45880110;