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GeneBe

12-107000045-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_004075.5(CRY1):c.722C>T(p.Ala241Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,609,466 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CRY1
NM_004075.5 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.90
Variant links:
Genes affected
CRY1 (HGNC:2384): (cryptochrome circadian regulator 1) 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. Loss of the related gene in mouse results in a shortened circadian cycle in complete darkness. [provided by RefSeq, Jan 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRY1NM_004075.5 linkuse as main transcriptc.722C>T p.Ala241Val missense_variant 6/13 ENST00000008527.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRY1ENST00000008527.10 linkuse as main transcriptc.722C>T p.Ala241Val missense_variant 6/131 NM_004075.5 P1
CRY1ENST00000546722.1 linkuse as main transcriptn.215C>T non_coding_transcript_exon_variant 3/33
CRY1ENST00000552790.5 linkuse as main transcriptn.1281C>T non_coding_transcript_exon_variant 8/132

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152058
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000810
AC:
2
AN:
246836
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
133140
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1457408
Hom.:
0
Cov.:
31
AF XY:
0.00000690
AC XY:
5
AN XY:
724580
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000355
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152058
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74268
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 15, 2023The c.722C>T (p.A241V) alteration is located in exon 6 (coding exon 6) of the CRY1 gene. This alteration results from a C to T substitution at nucleotide position 722, causing the alanine (A) at amino acid position 241 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Uncertain
0.075
D
BayesDel_noAF
Benign
-0.12
Cadd
Uncertain
25
Dann
Uncertain
1.0
DEOGEN2
Benign
0.25
T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.010
T
MetaRNN
Uncertain
0.45
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.17
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0080
D
Polyphen
0.89
P
Vest4
0.42
MVP
0.76
MPC
1.2
ClinPred
0.71
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.38
gMVP
0.77

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs1328030847; hg19: chr12-107393823; COSMIC: COSV50481104; COSMIC: COSV50481104; API