chr12-106991832-C-A

Variant names:

• chr12-106991832-C-A
• rs1056560
• NM_004075.5:c.*170G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001413458.1(CRY1):​c.*106G>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_001413458.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 18 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413458.1. 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.*170G>T		3_prime_UTR	Exon 13 of 13	NP_004066.1
	CRY1	NM_001413458.1		c.*106G>T		3_prime_UTR	Exon 13 of 13	NP_001400387.1
	CRY1	NM_001413459.1		c.*106G>T		3_prime_UTR	Exon 13 of 13	NP_001400388.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY1	ENST00000008527.10	TSL:1 MANE Select	c.*170G>T		3_prime_UTR	Exon 13 of 13	ENSP00000008527.5
	CRY1	ENST00000864076.1		c.*205G>T		3_prime_UTR	Exon 13 of 13	ENSP00000534135.1
	CRY1	ENST00000864077.1		c.*195G>T		3_prime_UTR	Exon 13 of 13	ENSP00000534136.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.533 AC: 226 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.342 AC: 14167 AN: 41414

American (AMR) AF: 0.591 AC: 9028 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1655 AN: 3468

East Asian (EAS) AF: 0.720 AC: 3723 AN: 5170

South Asian (SAS) AF: 0.577 AC: 2779 AN: 4814

European-Finnish (FIN) AF: 0.513 AC: 5399 AN: 10518

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38271 AN: 67880

Other (OTH) AF: 0.520 AC: 1095 AN: 2104

Alfa AF: 0.545 Hom.: 71288

Bravo AF: 0.504

Asia WGS AF: 0.605 AC: 2092 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	9.1
DANN	Benign	0.58
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs1056560; hg19: chr12-107385610;