chr12-106993385-C-G

Position:

• chr12-106993385-C-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY1	NM_004075.5	c.1586-349G>C		intron_variant		ENST00000008527.10	NP_004066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY1	ENST00000008527.10	c.1586-349G>C		intron_variant		1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000549356.1	c.146-349G>C		intron_variant		3		ENSP00000447738.1
CRY1	ENST00000552790.5	n.2165-349G>C		intron_variant		2

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

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.507

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.44

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: rs3741892; hg19: chr12-107387163;