12-107093134-C-G

Variant names:

• chr12-107093134-C-G
• rs3809237
• NM_004075.5:c.-173G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004075.5(CRY1):​c.-173G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRY1 NM_004075.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 8 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]

ENSG00000257548 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY1	NM_004075.5	MANE Select	c.-173G>C		5_prime_UTR	Exon 1 of 13	NP_004066.1	A2I2P0
	CRY1	NM_001413458.1		c.-173G>C		5_prime_UTR	Exon 1 of 13	NP_001400387.1
	CRY1	NM_001413459.1		c.-173G>C		5_prime_UTR	Exon 1 of 13	NP_001400388.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY1	ENST00000008527.10	TSL:1 MANE Select	c.-173G>C		5_prime_UTR	Exon 1 of 13	ENSP00000008527.5	Q16526
	CRY1	ENST00000864076.1		c.-173G>C		5_prime_UTR	Exon 1 of 13	ENSP00000534135.1
	CRY1	ENST00000864077.1		c.-173G>C		5_prime_UTR	Exon 1 of 13	ENSP00000534136.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152110 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 592988 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 301520

African (AFR) AF: 0.00 AC: 0 AN: 13888

American (AMR) AF: 0.00 AC: 0 AN: 14046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13572

East Asian (EAS) AF: 0.00 AC: 0 AN: 28280

South Asian (SAS) AF: 0.00 AC: 0 AN: 39658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2174

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 423688

Other (OTH) AF: 0.00 AC: 0 AN: 30184

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152110 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74282

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.8
DANN	Benign	0.87
PhyloP100		-2.2
PromoterAI		-0.024	Neutral

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: rs3809237; hg19: chr12-107486912;