chr12-107080184-G-T

Variant names:

• chr12-107080184-G-T
• rs10778528
• NM_004075.5:c.158+12620C>A

Variant summary

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

The NM_004075.5(CRY1):​c.158+12620C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,896 control chromosomes in the GnomAD database, including 23,269 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 (23269 hom., cov: 32)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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.158+12620C>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.158+12620C>A		intron_variant	Intron 1 of 12	1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000550633.1	n.711-7130C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83337 AN: 151778 Hom.: 23231 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.549 AC: 83430 AN: 151896 Hom.: 23269 Cov.: 32 AF XY: 0.551 AC XY: 40900 AN XY: 74232

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.551

Alfa AF: 0.581 Hom.: 50817

Bravo AF: 0.554

Asia WGS AF: 0.622 AC: 2164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.42

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: rs10778528; hg19: chr12-107473962;