12-107043028-C-T

Position:

• chr12-107043028-C-T

Variant summary

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

The NM_001413469.1(CRY1):​c.-431G>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 0.694 in 152,022 control chromosomes in the GnomAD database, including 37,472 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 0.69 (37463 hom., cov: 31)
  • Exomes 𝑓: 0.63 (9 hom.)
• Consequence: CRY1 NM_001413469.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY1	NM_004075.5	c.159-20836G>A		intron_variant		ENST00000008527.10	NP_004066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY1	ENST00000008527.10	c.159-20836G>A		intron_variant		1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000552790.5	n.639G>A		non_coding_transcript_exon_variant	3/13	2

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105403 AN: 151860 Hom.: 37402 Cov.: 31

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.759

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: 0.622

Gnomad OTH AF: 0.677

GnomAD4 exome AF: 0.630 AC: 29 AN: 46 Hom.: 9 Cov.: 0 AF XY: 0.553 AC XY: 21 AN XY: 38

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.694 AC: 105531 AN: 151976 Hom.: 37463 Cov.: 31 AF XY: 0.697 AC XY: 51801 AN XY: 74278

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.678

Alfa AF: 0.543 Hom.: 1583

Bravo AF: 0.713

Asia WGS AF: 0.835 AC: 2902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.88

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: rs2078074; hg19: chr12-107436806;