chr12-106991832-C-A

Position:

• chr12-106991832-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004075.5(CRY1):​c.*170G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,268 control chromosomes in the GnomAD database, including 20,353 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 0.51 (20289 hom., cov: 32)
  • Exomes 𝑓: 0.53 (64 hom.)
• Consequence: CRY1 NM_004075.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY1	NM_004075.5	c.*170G>T		3_prime_UTR_variant	13/13	ENST00000008527.10	NP_004066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY1	ENST00000008527	c.*170G>T		3_prime_UTR_variant	13/13	1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000552790.5	n.3369G>T		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76634 AN: 151722 Hom.: 20265 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.535 AC: 230 AN: 430 Hom.: 64 Cov.: 0 AF XY: 0.558 AC XY: 144 AN XY: 258

Gnomad4 FIN exome AF: 0.533

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.505 AC: 76708 AN: 151838 Hom.: 20289 Cov.: 32 AF XY: 0.509 AC XY: 37781 AN XY: 74170

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.520

Alfa AF: 0.549 Hom.: 28019

Bravo AF: 0.504

Asia WGS AF: 0.605 AC: 2092 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	9.1
DANN	Benign	0.58

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: rs1056560; hg19: chr12-107385610;