rs3809237

Variant names:

• chr12-107093134-C-A
• rs3809237
• NM_004075.5:c.-173G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-107093134-C-A
• chr12-107093134-C-G
• chr12-107093134-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004075.5(CRY1):​c.-173G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRY1 NM_004075.5 5_prime_UTR_premature_start_codon_gain
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRY1	NM_004075.5	c.-173G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 13	ENST00000008527.10	NP_004066.1
CRY1	NM_004075.5	c.-173G>T		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>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 13	1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000008527.10	c.-173G>T		5_prime_UTR_variant	Exon 1 of 13	1	NM_004075.5	ENSP00000008527.5
CRY1	ENST00000550633.1	n.380G>T		non_coding_transcript_exon_variant	Exon 1 of 2	3
ENSG00000257548	ENST00000547679.1	n.-164C>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 592990 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 301520

African (AFR) AF: 0.00 AC: 0 AN: 13888

American (AMR) AF: 0.00 AC: 0 AN: 14046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13572

East Asian (EAS) AF: 0.00 AC: 0 AN: 28282

South Asian (SAS) AF: 0.00 AC: 0 AN: 39658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2174

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 423688

Other (OTH) AF: 0.00 AC: 0 AN: 30184

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.6
DANN	Benign	0.92
PhyloP100		-2.2
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;