12-107025884-C-G

Position:

• chr12-107025884-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.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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRY1	NM_004075.5	c.159-3692G>C		intron_variant		ENST00000008527.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRY1	ENST00000008527.10	c.159-3692G>C		intron_variant		1	NM_004075.5	P1
CRY1	ENST00000552790.5	n.718-3692G>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.549

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.79
DANN	Benign	0.46

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: rs10861697; hg19: chr12-107419662;