11-45869957-A-G

Variant names:

• chr11-45869957-A-G
• rs4755345
• NM_021117.5:c.1195-96A>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.1195-96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 1,516,554 control chromosomes in the GnomAD database, including 640,446 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 0.88 (59891 hom., cov: 34)
  • Exomes 𝑓: 0.92 (580555 hom.)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 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.1195-96A>G		intron	N/A	NP_066940.3	A2I2P1
	CRY2	NM_001127457.3		c.1012-96A>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.1195-96A>G		intron	N/A	ENSP00000484684.1	Q49AN0-1
	CRY2	ENST00000443527.6	TSL:1	c.1258-96A>G		intron	N/A	ENSP00000406751.2	A0A0D2X7Z3
	CRY2	ENST00000616623.4	TSL:1	c.1258-96A>G		intron	N/A	ENSP00000478187.1	A0A0D2X7Z3

Frequencies

GnomAD3 genomes AF: 0.881 AC: 134075 AN: 152168 Hom.: 59852 Cov.: 34

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.882

GnomAD4 exome AF: 0.918 AC: 1252575 AN: 1364268 Hom.: 580555 Cov.: 31 AF XY: 0.917 AC XY: 614177 AN XY: 669672

African (AFR) AF: 0.806 AC: 24832 AN: 30790

American (AMR) AF: 0.875 AC: 29641 AN: 33858

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 19400 AN: 20698

East Asian (EAS) AF: 0.430 AC: 16738 AN: 38904

South Asian (SAS) AF: 0.874 AC: 63400 AN: 72526

European-Finnish (FIN) AF: 0.946 AC: 37750 AN: 39894

Middle Eastern (MID) AF: 0.883 AC: 3439 AN: 3894

European-Non Finnish (NFE) AF: 0.943 AC: 1006296 AN: 1067300

Other (OTH) AF: 0.906 AC: 51079 AN: 56404

GnomAD4 genome AF: 0.881 AC: 134171 AN: 152286 Hom.: 59891 Cov.: 34 AF XY: 0.879 AC XY: 65463 AN XY: 74468

African (AFR) AF: 0.811 AC: 33669 AN: 41532

American (AMR) AF: 0.891 AC: 13646 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3251 AN: 3472

East Asian (EAS) AF: 0.457 AC: 2359 AN: 5158

South Asian (SAS) AF: 0.860 AC: 4150 AN: 4828

European-Finnish (FIN) AF: 0.950 AC: 10092 AN: 10624

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.940 AC: 63987 AN: 68042

Other (OTH) AF: 0.882 AC: 1865 AN: 2114

Alfa AF: 0.917 Hom.: 78181

Bravo AF: 0.870

Asia WGS AF: 0.758 AC: 2640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.66
PhyloP100		2.0
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: rs4755345; hg19: chr11-45891508; COSMIC: COSV69888642; COSMIC: COSV69888642;