rs10861688

Positions:

• chr12-107000270-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004075.5(CRY1):​c.685-188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,978 control chromosomes in the GnomAD database, including 1,990 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 0.15 (1990 hom., cov: 32)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY1	NM_004075.5	c.685-188G>A		intron_variant		ENST00000008527.10	NP_004066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY1	ENST00000008527.10	c.685-188G>A		intron_variant		1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000546722.1	n.178-188G>A		intron_variant		3
CRY1	ENST00000552790.5	n.1244-188G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22449 AN: 151864 Hom.: 1989 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.148 AC: 22455 AN: 151978 Hom.: 1990 Cov.: 32 AF XY: 0.148 AC XY: 11016 AN XY: 74284

Gnomad4 AFR AF: 0.0582

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.165

Alfa AF: 0.183 Hom.: 5491

Bravo AF: 0.143

Asia WGS AF: 0.241 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs10861688; hg19: chr12-107394048;