chr12-107074051-T-A

Variant names:

• chr12-107074051-T-A
• rs7294758
• NM_004075.5:c.158+18753A>T

Variant summary

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

The NM_001413458.1(CRY1):​c.158+18753A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 152,248 control chromosomes in the GnomAD database, including 274 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 0.044 (274 hom., cov: 32)
• Consequence: CRY1 NM_001413458.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413458.1. 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+18753A>T		intron	N/A	NP_004066.1
	CRY1	NM_001413458.1		c.158+18753A>T		intron	N/A	NP_001400387.1
	CRY1	NM_001413459.1		c.158+18753A>T		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+18753A>T		intron	N/A	ENSP00000008527.5
	CRY1	ENST00000864076.1		c.158+18753A>T		intron	N/A	ENSP00000534135.1
	CRY1	ENST00000864077.1		c.158+18753A>T		intron	N/A	ENSP00000534136.1

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6622 AN: 152130 Hom.: 271 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.00649

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0301

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

GnomAD4 genome AF: 0.0436 AC: 6639 AN: 152248 Hom.: 274 Cov.: 32 AF XY: 0.0413 AC XY: 3073 AN XY: 74456

African (AFR) AF: 0.111 AC: 4614 AN: 41526

American (AMR) AF: 0.0251 AC: 384 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5188

South Asian (SAS) AF: 0.00766 AC: 37 AN: 4828

European-Finnish (FIN) AF: 0.00649 AC: 69 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0210 AC: 1429 AN: 68004

Other (OTH) AF: 0.0298 AC: 63 AN: 2116

Alfa AF: 0.0325 Hom.: 20

Bravo AF: 0.0492

Asia WGS AF: 0.0140 AC: 49 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.59
PhyloP100		-0.045
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: rs7294758; hg19: chr12-107467829;