12-107017827-C-T

Variant names:

• chr12-107017827-C-T
• rs1921126
• NM_004075.5:c.267+4257G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004075.5(CRY1):​c.267+4257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,066 control chromosomes in the GnomAD database, including 23,049 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 0.55 (23049 hom., cov: 32)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY1	NM_004075.5	c.267+4257G>A		intron_variant	Intron 2 of 12	ENST00000008527.10	NP_004066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRY1	ENST00000008527.10	c.267+4257G>A		intron_variant	Intron 2 of 12	1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000552790.5	n.826+4257G>A		intron_variant	Intron 4 of 12	2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82928 AN: 151948 Hom.: 23011 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.548

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.546 AC: 83018 AN: 152066 Hom.: 23049 Cov.: 32 AF XY: 0.548 AC XY: 40731 AN XY: 74330

African (AFR) AF: 0.444 AC: 18418 AN: 41472

American (AMR) AF: 0.616 AC: 9406 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1660 AN: 3472

East Asian (EAS) AF: 0.726 AC: 3756 AN: 5172

South Asian (SAS) AF: 0.585 AC: 2822 AN: 4828

European-Finnish (FIN) AF: 0.518 AC: 5465 AN: 10554

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.584 AC: 39727 AN: 67974

Other (OTH) AF: 0.547 AC: 1157 AN: 2114

Alfa AF: 0.554 Hom.: 3285

Bravo AF: 0.550

Asia WGS AF: 0.621 AC: 2160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.24
PhyloP100		0.36
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: rs1921126; hg19: chr12-107411605;