chr12-107075190-A-G

Position:

• chr12-107075190-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004075.5(CRY1):​c.158+17614T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 152,332 control chromosomes in the GnomAD database, including 114 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 0.037 (114 hom., cov: 32)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814

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=-0.97).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0371 (5646/152332) while in subpopulation NFE AF= 0.0473 (3217/68032). AF 95% confidence interval is 0.0459. There are 114 homozygotes in gnomad4. There are 2656 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5646 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRY1	NM_004075.5	c.158+17614T>C		intron_variant		ENST00000008527.10	NP_004066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRY1	ENST00000008527.10	c.158+17614T>C		intron_variant		1	NM_004075.5	ENSP00000008527	P1
CRY1	ENST00000550633.1	n.711-2136T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5641 AN: 152214 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.0334

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

GnomAD4 genome AF: 0.0371 AC: 5646 AN: 152332 Hom.: 114 Cov.: 32 AF XY: 0.0357 AC XY: 2656 AN XY: 74492

Gnomad4 AFR AF: 0.0322

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.0476

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.0415

Gnomad4 NFE AF: 0.0473

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0439 Hom.: 39

Bravo AF: 0.0356

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.55
DANN	Benign	0.44

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: rs17289712; hg19: chr12-107468968;