rs10746083

Variant names:

• chr12-107060374-T-C
• rs10746083
• NM_004075.5:c.158+32430A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004075.5(CRY1):​c.158+32430A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,864 control chromosomes in the GnomAD database, including 20,069 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 0.50 (20069 hom., cov: 32)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

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.158+32430A>G		intron	N/A	NP_004066.1
	CRY1	NM_001413458.1		c.158+32430A>G		intron	N/A	NP_001400387.1
	CRY1	NM_001413459.1		c.158+32430A>G		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.158+32430A>G		intron	N/A	ENSP00000008527.5

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76209 AN: 151746 Hom.: 20044 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.502 AC: 76285 AN: 151864 Hom.: 20069 Cov.: 32 AF XY: 0.507 AC XY: 37591 AN XY: 74216

African (AFR) AF: 0.341 AC: 14144 AN: 41418

American (AMR) AF: 0.589 AC: 8976 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1647 AN: 3468

East Asian (EAS) AF: 0.723 AC: 3722 AN: 5150

South Asian (SAS) AF: 0.577 AC: 2778 AN: 4816

European-Finnish (FIN) AF: 0.510 AC: 5367 AN: 10524

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.559 AC: 37967 AN: 67926

Other (OTH) AF: 0.517 AC: 1095 AN: 2116

Alfa AF: 0.509 Hom.: 2758

Bravo AF: 0.504

Asia WGS AF: 0.605 AC: 2103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.82
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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: rs10746083; hg19: chr12-107454152;