12-107046525-C-T

Variant names:

• chr12-107046525-C-T
• rs59790130
• NM_004075.5:c.159-24333G>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.159-24333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 151,996 control chromosomes in the GnomAD database, including 1,964 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 0.12 (1964 hom., cov: 32)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY1	NM_004075.5	c.159-24333G>A		intron_variant	Intron 1 of 12	ENST00000008527.10	NP_004066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRY1	ENST00000008527.10	c.159-24333G>A		intron_variant	Intron 1 of 12	1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000552790.5	n.488+3246G>A		intron_variant	Intron 2 of 12	2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18806 AN: 151880 Hom.: 1962 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.124 AC: 18832 AN: 151996 Hom.: 1964 Cov.: 32 AF XY: 0.126 AC XY: 9356 AN XY: 74268

African (AFR) AF: 0.271 AC: 11249 AN: 41436

American (AMR) AF: 0.135 AC: 2062 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3472

East Asian (EAS) AF: 0.227 AC: 1174 AN: 5162

South Asian (SAS) AF: 0.127 AC: 613 AN: 4820

European-Finnish (FIN) AF: 0.0637 AC: 671 AN: 10540

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0372 AC: 2528 AN: 67984

Other (OTH) AF: 0.113 AC: 238 AN: 2114

Alfa AF: 0.0819 Hom.: 118

Bravo AF: 0.135

Asia WGS AF: 0.199 AC: 689 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.46
PhyloP100		0.28
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: rs59790130; hg19: chr12-107440303;