rs17289712

Variant names:

• chr12-107075190-A-G
• rs17289712
• NM_004075.5:c.158+17614T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004075.5(CRY1):​c.158+17614T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 152,332 control chromosomes in the GnomAD database, including 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 0.037 (114 hom., cov: 32)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814
• Publications: 4 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=-0.97).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0371 (5646/152332) while in subpopulation NFE AF = 0.0473 (3217/68032). AF 95% confidence interval is 0.0459. There are 114 homozygotes in GnomAd4. There are 2656 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5646 AD gene.

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.158+17614T>C		intron	N/A	NP_004066.1	A2I2P0
	CRY1	NM_001413458.1		c.158+17614T>C		intron	N/A	NP_001400387.1
	CRY1	NM_001413459.1		c.158+17614T>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.158+17614T>C		intron	N/A	ENSP00000008527.5	Q16526
	CRY1	ENST00000864076.1		c.158+17614T>C		intron	N/A	ENSP00000534135.1
	CRY1	ENST00000864077.1		c.158+17614T>C		intron	N/A	ENSP00000534136.1

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5641 AN: 152214 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.0334

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

GnomAD4 genome AF: 0.0371 AC: 5646 AN: 152332 Hom.: 114 Cov.: 32 AF XY: 0.0357 AC XY: 2656 AN XY: 74492

African (AFR) AF: 0.0322 AC: 1337 AN: 41574

American (AMR) AF: 0.0191 AC: 292 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 165 AN: 3470

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5186

South Asian (SAS) AF: 0.00891 AC: 43 AN: 4828

European-Finnish (FIN) AF: 0.0415 AC: 441 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0473 AC: 3217 AN: 68032

Other (OTH) AF: 0.0331 AC: 70 AN: 2116

Alfa AF: 0.0452 Hom.: 206

Bravo AF: 0.0356

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.55
DANN	Benign	0.44
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism

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: rs17289712; hg19: chr12-107468968;