rs10437895

Variant names:

• chr12-107047046-C-T
• rs10437895
• NM_004075.5:c.159-24854G>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.159-24854G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,012 control chromosomes in the GnomAD database, including 19,285 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 0.48 (19285 hom., cov: 33)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720
• Publications: 1 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY1	NM_004075.5	c.159-24854G>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.159-24854G>A		intron_variant	Intron 1 of 12	1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000552790.5	n.488+2725G>A		intron_variant	Intron 2 of 12	2

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73558 AN: 151894 Hom.: 19269 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.484 AC: 73605 AN: 152012 Hom.: 19285 Cov.: 33 AF XY: 0.489 AC XY: 36333 AN XY: 74290

African (AFR) AF: 0.271 AC: 11237 AN: 41454

American (AMR) AF: 0.582 AC: 8903 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1656 AN: 3472

East Asian (EAS) AF: 0.723 AC: 3740 AN: 5174

South Asian (SAS) AF: 0.568 AC: 2734 AN: 4812

European-Finnish (FIN) AF: 0.513 AC: 5414 AN: 10548

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38264 AN: 67954

Other (OTH) AF: 0.507 AC: 1068 AN: 2106

Alfa AF: 0.503 Hom.: 2550

Bravo AF: 0.481

Asia WGS AF: 0.595 AC: 2070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.81
PhyloP100		-0.72
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: rs10437895; hg19: chr12-107440824;