12-107093134-C-T

Variant names:

• chr12-107093134-C-T
• rs3809237
• NM_004075.5:c.-173G>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.-173G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 743,534 control chromosomes in the GnomAD database, including 164,217 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 0.70 (37660 hom., cov: 33)
  • Exomes 𝑓: 0.65 (126557 hom.)
• Consequence: CRY1 NM_004075.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 8 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY1	NM_004075.5	c.-173G>A		5_prime_UTR_variant	Exon 1 of 13	ENST00000008527.10	NP_004066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRY1	ENST00000008527.10	c.-173G>A		5_prime_UTR_variant	Exon 1 of 13	1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000550633.1	n.380G>A		non_coding_transcript_exon_variant	Exon 1 of 2	3
ENSG00000257548	ENST00000547679.1	n.-164C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105771 AN: 152074 Hom.: 37598 Cov.: 33

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.678

GnomAD4 exome AF: 0.647 AC: 382666 AN: 591340 Hom.: 126557 Cov.: 8 AF XY: 0.650 AC XY: 195405 AN XY: 300704

African (AFR) AF: 0.800 AC: 11085 AN: 13858

American (AMR) AF: 0.776 AC: 10890 AN: 14034

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 7354 AN: 13558

East Asian (EAS) AF: 0.952 AC: 26919 AN: 28282

South Asian (SAS) AF: 0.716 AC: 28318 AN: 39570

European-Finnish (FIN) AF: 0.577 AC: 15833 AN: 27462

Middle Eastern (MID) AF: 0.666 AC: 1446 AN: 2172

European-Non Finnish (NFE) AF: 0.618 AC: 260764 AN: 422282

Other (OTH) AF: 0.666 AC: 20057 AN: 30122

GnomAD4 genome AF: 0.696 AC: 105901 AN: 152194 Hom.: 37660 Cov.: 33 AF XY: 0.698 AC XY: 51939 AN XY: 74390

African (AFR) AF: 0.798 AC: 33177 AN: 41550

American (AMR) AF: 0.761 AC: 11642 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1911 AN: 3468

East Asian (EAS) AF: 0.968 AC: 4995 AN: 5160

South Asian (SAS) AF: 0.714 AC: 3447 AN: 4830

European-Finnish (FIN) AF: 0.582 AC: 6156 AN: 10580

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42470 AN: 67982

Other (OTH) AF: 0.680 AC: 1437 AN: 2114

Alfa AF: 0.664 Hom.: 14352

Bravo AF: 0.714

Asia WGS AF: 0.835 AC: 2901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.7
DANN	Benign	0.96
PhyloP100		-2.2
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3809237; hg19: chr12-107486912;