rs10861697

Variant names:

• chr12-107025884-C-A
• rs10861697
• NM_004075.5:c.159-3692G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-107025884-C-A
• chr12-107025884-C-G
• chr12-107025884-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004075.5(CRY1):​c.159-3692G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 150,462 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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>T		intron	N/A	NP_004066.1
	CRY1	NM_001413458.1		c.159-3692G>T		intron	N/A	NP_001400387.1
	CRY1	NM_001413459.1		c.159-3692G>T		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>T		intron	N/A	ENSP00000008527.5
	CRY1	ENST00000552790.5	TSL:2	n.718-3692G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000665 AC: 1 AN: 150462 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000665 AC: 1 AN: 150462 Hom.: 0 Cov.: 26 AF XY: 0.0000137 AC XY: 1 AN XY: 73206

African (AFR) AF: 0.00 AC: 0 AN: 40800

American (AMR) AF: 0.00 AC: 0 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5056

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67840

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.00 Hom.: 1101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.72
DANN	Benign	0.39
PhyloP100		-0.58

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;