rs11605924

Variant names:

• chr11-45851540-A-C
• rs11605924
• NM_021117.5:c.215+3835A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 147 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 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.215+3835A>C		intron	N/A	NP_066940.3	A2I2P1
	CRY2	NM_001127457.3		c.32+4259A>C		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.215+3835A>C		intron	N/A	ENSP00000484684.1	Q49AN0-1
	CRY2	ENST00000443527.6	TSL:1	c.278+3835A>C		intron	N/A	ENSP00000406751.2	A0A0D2X7Z3
	CRY2	ENST00000616623.4	TSL:1	c.278+3835A>C		intron	N/A	ENSP00000478187.1	A0A0D2X7Z3

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

African (AFR) AF: 0.128 AC: 5307 AN: 41512

American (AMR) AF: 0.501 AC: 7646 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1990 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1257 AN: 5178

South Asian (SAS) AF: 0.503 AC: 2425 AN: 4818

European-Finnish (FIN) AF: 0.477 AC: 5027 AN: 10548

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35366 AN: 67986

Other (OTH) AF: 0.437 AC: 922 AN: 2110

Alfa AF: 0.483 Hom.: 65279

Bravo AF: 0.387

Asia WGS AF: 0.396 AC: 1381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		-0.12
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11605924;

hg19: chr11-45873091;