12-106993385-C-G

Variant names:

• chr12-106993385-C-G
• rs3741892
• NM_004075.5:c.1586-349G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004075.5(CRY1):​c.1586-349G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,020 control chromosomes in the GnomAD database, including 19,114 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 0.48 (19114 hom., cov: 27)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 7 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004075.5. 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
	CRY1	NM_004075.5	MANE Select	c.1586-349G>C		intron	N/A	NP_004066.1	A2I2P0
	CRY1	NM_001413458.1		c.1586-349G>C		intron	N/A	NP_001400387.1
	CRY1	NM_001413459.1		c.1586-349G>C		intron	N/A	NP_001400388.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY1	ENST00000008527.10	TSL:1 MANE Select	c.1586-349G>C		intron	N/A	ENSP00000008527.5	Q16526
	CRY1	ENST00000864076.1		c.1586-349G>C		intron	N/A	ENSP00000534135.1
	CRY1	ENST00000864077.1		c.1586-349G>C		intron	N/A	ENSP00000534136.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73011 AN: 150900 Hom.: 19097 Cov.: 27

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.507

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.484 AC: 73060 AN: 151020 Hom.: 19114 Cov.: 27 AF XY: 0.488 AC XY: 35948 AN XY: 73672

African (AFR) AF: 0.270 AC: 11128 AN: 41150

American (AMR) AF: 0.581 AC: 8798 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1652 AN: 3466

East Asian (EAS) AF: 0.722 AC: 3653 AN: 5062

South Asian (SAS) AF: 0.566 AC: 2690 AN: 4752

European-Finnish (FIN) AF: 0.511 AC: 5298 AN: 10364

Middle Eastern (MID) AF: 0.555 AC: 161 AN: 290

European-Non Finnish (NFE) AF: 0.563 AC: 38190 AN: 67796

Other (OTH) AF: 0.507 AC: 1064 AN: 2100

Alfa AF: 0.512 Hom.: 2514

Bravo AF: 0.481

Asia WGS AF: 0.594 AC: 2067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.44
PhyloP100		0.43
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: rs3741892; hg19: chr12-107387163;