Genetic Variant NM_004075.5:c.-308C>T (chr12-107093269-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004075.5(CRY1):c.-308C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 307,566 control chromosomes in the GnomAD database, including 3,349 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 0.14 ( 2591 hom., cov: 34)

Exomes 𝑓: 0.068 ( 758 hom. )

Consequence

CRY1
NM_004075.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.153

Publications

10 publications found

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]

CRY1 links:

ENSG00000257548 (HGNC:):

ENSG00000257548 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY1	NM_004075.5 link	c.-308C>T		5_prime_UTR_variant	Exon 1 of 13	ENST00000008527.10	NP_004066.1	Q16526A2I2P0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRY1	ENST00000008527.10 link	c.-308C>T	5_prime_UTR_variant	Exon 1 of 13	1	NM_004075.5	ENSP00000008527.5	Q16526
CRY1	ENST00000550633.1 link	n.245C>T	non_coding_transcript_exon_variant	Exon 1 of 2	3
ENSG00000257548	ENST00000547679.1 link	n.-29G>A	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20951

AN:

152128

Hom.:

2589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.0732

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0634

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0373

Gnomad OTH

AF:

0.120

GnomAD4 exome

AF:

0.0682

AC:

10598

AN:

155322

Hom.:

758

Cov.:

AF XY:

0.0657

AC XY:

5161

AN XY:

78508

show subpopulations

African (AFR)

AF:

0.306

AC:

1397

AN:

4558

American (AMR)

AF:

0.139

AC:

903

AN:

6480

Ashkenazi Jewish (ASJ)

AF:

0.0695

AC:

400

AN:

5756

East Asian (EAS)

AF:

0.193

AC:

2392

AN:

12376

South Asian (SAS)

AF:

0.0984

AC:

601

AN:

6108

European-Finnish (FIN)

AF:

0.0554

AC:

511

AN:

9228

Middle Eastern (MID)

AF:

0.0988

AC:

AN:

810

European-Non Finnish (NFE)

AF:

0.0341

AC:

3397

AN:

99516

Other (OTH)

AF:

0.0874

AC:

917

AN:

10490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

443

886

1329

1772

2215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.138

AC:

20979

AN:

152244

Hom.:

2591

Cov.:

AF XY:

0.139

AC XY:

10341

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.319

AC:

13265

AN:

41536

American (AMR)

AF:

0.141

AC:

2157

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0732

AC:

254

AN:

3472

East Asian (EAS)

AF:

0.228

AC:

1176

AN:

5166

South Asian (SAS)

AF:

0.128

AC:

620

AN:

4830

European-Finnish (FIN)

AF:

0.0634

AC:

673

AN:

10614

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0373

AC:

2535

AN:

68002

Other (OTH)

AF:

0.121

AC:

256

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

804

1609

2413

3218

4022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0684

Hom.:

386

Bravo

AF:

0.151

Asia WGS

AF:

0.200

AC:

694

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.15

PromoterAI

0.042

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over