12-107047774-A-C

Variant names:

• chr12-107047774-A-C
• rs10746077
• NM_004075.5:c.159-25582T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004075.5(CRY1):​c.159-25582T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 152,036 control chromosomes in the GnomAD database, including 2 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 0.0019 (2 hom., cov: 31)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BS2: High AC in GnomAd4 at 291 AD gene.

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.159-25582T>G		intron	N/A	NP_004066.1
	CRY1	NM_001413458.1		c.159-25582T>G		intron	N/A	NP_001400387.1
	CRY1	NM_001413459.1		c.159-25582T>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.159-25582T>G		intron	N/A	ENSP00000008527.5
	CRY1	ENST00000552790.5	TSL:2	n.488+1997T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 293 AN: 151918 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00665

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000959

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

GnomAD4 genome AF: 0.00191 AC: 291 AN: 152036 Hom.: 2 Cov.: 31 AF XY: 0.00172 AC XY: 128 AN XY: 74284

African (AFR) AF: 0.00661 AC: 274 AN: 41472

American (AMR) AF: 0.000916 AC: 14 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67950

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00 Hom.: 1552

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.6
DANN	Benign	0.35
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10746077; hg19: chr12-107441552;