12-107025884-C-G

Variant names:

• chr12-107025884-C-G
• rs10861697
• NM_004075.5:c.159-3692G>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.159-3692G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 150,404 control chromosomes in the GnomAD database, including 22,930 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 0.55 (22930 hom., cov: 26)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY1	NM_004075.5	MANE Select	c.159-3692G>C		intron	N/A	NP_004066.1
	CRY1	NM_001413458.1		c.159-3692G>C		intron	N/A	NP_001400387.1
	CRY1	NM_001413459.1		c.159-3692G>C		intron	N/A	NP_001400388.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY1	ENST00000008527.10	TSL:1 MANE Select	c.159-3692G>C		intron	N/A	ENSP00000008527.5
	CRY1	ENST00000552790.5	TSL:2	n.718-3692G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.548 AC: 82320 AN: 150290 Hom.: 22894 Cov.: 26

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.548 AC: 82408 AN: 150404 Hom.: 22930 Cov.: 26 AF XY: 0.549 AC XY: 40221 AN XY: 73232

African (AFR) AF: 0.452 AC: 18483 AN: 40880

American (AMR) AF: 0.615 AC: 9174 AN: 14916

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1656 AN: 3462

East Asian (EAS) AF: 0.726 AC: 3662 AN: 5042

South Asian (SAS) AF: 0.583 AC: 2793 AN: 4788

European-Finnish (FIN) AF: 0.515 AC: 5291 AN: 10276

Middle Eastern (MID) AF: 0.562 AC: 163 AN: 290

European-Non Finnish (NFE) AF: 0.584 AC: 39597 AN: 67762

Other (OTH) AF: 0.549 AC: 1141 AN: 2078

Alfa AF: 0.421 Hom.: 1101

Bravo AF: 0.553

Asia WGS AF: 0.622 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.79
DANN	Benign	0.46
PhyloP100		-0.58
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: rs10861697; hg19: chr12-107419662;