12-107093269-G-A

Variant names:

• chr12-107093269-G-A
• rs3809236
• NM_004075.5:c.-308C>T

Variant summary

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

The NM_004075.5(CRY1):​c.-308C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 307,566 control chromosomes in the GnomAD database, including 3,349 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 0.14 (2591 hom., cov: 34)
  • Exomes 𝑓: 0.068 (758 hom.)
• Consequence: CRY1 NM_004075.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 10 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]

ENSG00000257548 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004075.5. 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.-308C>T		5_prime_UTR	Exon 1 of 13	NP_004066.1
	CRY1	NR_182152.1		n.281C>T		non_coding_transcript_exon	Exon 1 of 13
	CRY1	NR_182153.1		n.281C>T		non_coding_transcript_exon	Exon 1 of 12

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY1	ENST00000008527.10	TSL:1 MANE Select	c.-308C>T		5_prime_UTR	Exon 1 of 13	ENSP00000008527.5
	CRY1	ENST00000550633.1	TSL:3	n.245C>T		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000257548	ENST00000547679.1	TSL:3	n.-29G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20951 AN: 152128 Hom.: 2589 Cov.: 34

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0634

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.0682 AC: 10598 AN: 155322 Hom.: 758 Cov.: 0 AF XY: 0.0657 AC XY: 5161 AN XY: 78508

African (AFR) AF: 0.306 AC: 1397 AN: 4558

American (AMR) AF: 0.139 AC: 903 AN: 6480

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 400 AN: 5756

East Asian (EAS) AF: 0.193 AC: 2392 AN: 12376

South Asian (SAS) AF: 0.0984 AC: 601 AN: 6108

European-Finnish (FIN) AF: 0.0554 AC: 511 AN: 9228

Middle Eastern (MID) AF: 0.0988 AC: 80 AN: 810

European-Non Finnish (NFE) AF: 0.0341 AC: 3397 AN: 99516

Other (OTH) AF: 0.0874 AC: 917 AN: 10490

GnomAD4 genome AF: 0.138 AC: 20979 AN: 152244 Hom.: 2591 Cov.: 34 AF XY: 0.139 AC XY: 10341 AN XY: 74448

African (AFR) AF: 0.319 AC: 13265 AN: 41536

American (AMR) AF: 0.141 AC: 2157 AN: 15306

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

East Asian (EAS) AF: 0.228 AC: 1176 AN: 5166

South Asian (SAS) AF: 0.128 AC: 620 AN: 4830

European-Finnish (FIN) AF: 0.0634 AC: 673 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0373 AC: 2535 AN: 68002

Other (OTH) AF: 0.121 AC: 256 AN: 2112

Alfa AF: 0.0684 Hom.: 386

Bravo AF: 0.151

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		0.15
PromoterAI		0.042	Neutral
Mutation Taster		=300/0	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: rs3809236; hg19: chr12-107487047;