11-45881643-A-G

Variant names:

• chr11-45881643-A-G
• rs10838527
• NM_021117.5:c.*732A>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.*732A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,214 control chromosomes in the GnomAD database, including 1,504 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 0.12 (1504 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRY2 NM_021117.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 24 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY2	NM_021117.5	MANE Select	c.*732A>G		3_prime_UTR	Exon 12 of 12	NP_066940.3
	CRY2	NM_001127457.3		c.*732A>G		3_prime_UTR	Exon 12 of 12	NP_001120929.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY2	ENST00000616080.2	TSL:1 MANE Select	c.*732A>G		3_prime_UTR	Exon 12 of 12	ENSP00000484684.1
	CRY2	ENST00000443527.6	TSL:1	c.*732A>G		3_prime_UTR	Exon 12 of 12	ENSP00000406751.2
	CRY2	ENST00000616623.4	TSL:1	c.*732A>G		3_prime_UTR	Exon 12 of 12	ENSP00000478187.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18158 AN: 152096 Hom.: 1500 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.105

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 20 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.119 AC: 18174 AN: 152214 Hom.: 1504 Cov.: 33 AF XY: 0.119 AC XY: 8839 AN XY: 74432

African (AFR) AF: 0.233 AC: 9677 AN: 41500

American (AMR) AF: 0.0806 AC: 1234 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4824

European-Finnish (FIN) AF: 0.118 AC: 1248 AN: 10594

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0820 AC: 5574 AN: 68014

Other (OTH) AF: 0.104 AC: 219 AN: 2114

Alfa AF: 0.0880 Hom.: 1400

Bravo AF: 0.120

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.4
DANN	Benign	0.83
PhyloP100		-0.51
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: rs10838527; hg19: chr11-45903194;