rs7123390

Variant names:

• chr11-45869867-G-A
• rs7123390
• NM_021117.5:c.1194+50G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021117.5(CRY2):​c.1194+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,548,998 control chromosomes in the GnomAD database, including 51,496 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 0.22 (3979 hom., cov: 33)
  • Exomes 𝑓: 0.26 (47517 hom.)
• Consequence: CRY2 NM_021117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 21 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 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.1194+50G>A		intron	N/A	NP_066940.3	A2I2P1
	CRY2	NM_001127457.3		c.1011+50G>A		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.1194+50G>A		intron	N/A	ENSP00000484684.1	Q49AN0-1
	CRY2	ENST00000443527.6	TSL:1	c.1257+50G>A		intron	N/A	ENSP00000406751.2	A0A0D2X7Z3
	CRY2	ENST00000616623.4	TSL:1	c.1257+50G>A		intron	N/A	ENSP00000478187.1	A0A0D2X7Z3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32953 AN: 152040 Hom.: 3982 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.214

GnomAD2 exomes AF: 0.216 AC: 42255 AN: 195384 AF XY: 0.220

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.129

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.257 AC: 358728 AN: 1396840 Hom.: 47517 Cov.: 32 AF XY: 0.255 AC XY: 175383 AN XY: 687442

African (AFR) AF: 0.127 AC: 4056 AN: 32000

American (AMR) AF: 0.123 AC: 4779 AN: 38786

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 6048 AN: 22116

East Asian (EAS) AF: 0.144 AC: 5634 AN: 39056

South Asian (SAS) AF: 0.185 AC: 14398 AN: 77678

European-Finnish (FIN) AF: 0.275 AC: 12687 AN: 46156

Middle Eastern (MID) AF: 0.213 AC: 1099 AN: 5154

European-Non Finnish (NFE) AF: 0.274 AC: 295997 AN: 1078388

Other (OTH) AF: 0.244 AC: 14030 AN: 57506

GnomAD4 genome AF: 0.217 AC: 32952 AN: 152158 Hom.: 3979 Cov.: 33 AF XY: 0.215 AC XY: 15967 AN XY: 74372

African (AFR) AF: 0.132 AC: 5492 AN: 41538

American (AMR) AF: 0.167 AC: 2549 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3464

East Asian (EAS) AF: 0.128 AC: 662 AN: 5164

South Asian (SAS) AF: 0.177 AC: 855 AN: 4826

European-Finnish (FIN) AF: 0.287 AC: 3034 AN: 10588

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18652 AN: 67964

Other (OTH) AF: 0.213 AC: 450 AN: 2112

Alfa AF: 0.251 Hom.: 7577

Bravo AF: 0.204

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.65
PhyloP100		-0.078
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: rs7123390; hg19: chr11-45891418; COSMIC: COSV69889074; COSMIC: COSV69889074;