12-107093134-C-T

Position:

• chr12-107093134-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004075.5(CRY1):​c.-173G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 743,534 control chromosomes in the GnomAD database, including 164,217 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 0.70 (37660 hom., cov: 33)
  • Exomes 𝑓: 0.65 (126557 hom.)
• Consequence: CRY1 NM_004075.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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]

CRY1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY1	NM_004075.5	c.-173G>A		5_prime_UTR_variant	1/13	ENST00000008527.10	NP_004066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY1	ENST00000008527.10	c.-173G>A		5_prime_UTR_variant	1/13	1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000550633.1	n.380G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105771 AN: 152074 Hom.: 37598 Cov.: 33

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.678

GnomAD4 exome AF: 0.647 AC: 382666 AN: 591340 Hom.: 126557 Cov.: 8 AF XY: 0.650 AC XY: 195405 AN XY: 300704

Gnomad4 AFR exome AF: 0.800

Gnomad4 AMR exome AF: 0.776

Gnomad4 ASJ exome AF: 0.542

Gnomad4 EAS exome AF: 0.952

Gnomad4 SAS exome AF: 0.716

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.618

Gnomad4 OTH exome AF: 0.666

GnomAD4 genome AF: 0.696 AC: 105901 AN: 152194 Hom.: 37660 Cov.: 33 AF XY: 0.698 AC XY: 51939 AN XY: 74390

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.680

Alfa AF: 0.662 Hom.: 11540

Bravo AF: 0.714

Asia WGS AF: 0.835 AC: 2901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.7
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3809237; hg19: chr12-107486912;