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rs35488012

chr11-45867677-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_021117.5(CRY2):c.807C>T(p.Gly269=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,614,258 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 40 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 31 hom. )

Consequence

CRY2
NM_021117.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.897
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-45867677-C-T is Benign according to our data. Variant chr11-45867677-C-T is described in ClinVar as [Benign]. Clinvar id is 780966.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.897 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1743/152368) while in subpopulation AFR AF= 0.0402 (1671/41580). AF 95% confidence interval is 0.0386. There are 40 homozygotes in gnomad4. There are 838 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1744 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRY2NM_021117.5 linkuse as main transcriptc.807C>T p.Gly269= synonymous_variant 6/12 ENST00000616080.2
CRY2NM_001127457.3 linkuse as main transcriptc.624C>T p.Gly208= synonymous_variant 6/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRY2ENST00000616080.2 linkuse as main transcriptc.807C>T p.Gly269= synonymous_variant 6/121 NM_021117.5 P2Q49AN0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0115
AC:
1744
AN:
152250
Hom.:
41
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0403
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00366
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00313
AC:
786
AN:
251474
Hom.:
17
AF XY:
0.00238
AC XY:
324
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.0423
Gnomad AMR exome
AF:
0.00257
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.00114
AC:
1660
AN:
1461890
Hom.:
31
Cov.:
30
AF XY:
0.000993
AC XY:
722
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0401
Gnomad4 AMR exome
AF:
0.00241
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000270
Gnomad4 OTH exome
AF:
0.00278
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0114
AC:
1743
AN:
152368
Hom.:
40
Cov.:
33
AF XY:
0.0112
AC XY:
838
AN XY:
74516
show subpopulations
Gnomad4 AFR
AF:
0.0402
Gnomad4 AMR
AF:
0.00366
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00493
Hom.:
5
Bravo
AF:
0.0127
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 13, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.26
Cadd
Benign
14
Dann
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35488012; hg19: chr11-45889228; API