rs11932595

Variant names:

• chr4-55457430-A-G
• rs11932595
• NM_004898.4:c.793-1130T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-55457430-A-G
• chr4-55457430-A-T

Variant summary

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

The NM_004898.4(CLOCK):​c.793-1130T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,946 control chromosomes in the GnomAD database, including 11,698 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 0.39 (11698 hom., cov: 31)
• Consequence: CLOCK NM_004898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596
• Publications: 76 publications found

Genes affected

CLOCK (HGNC:2082): (clock circadian regulator) The protein encoded by this gene plays a central role in the regulation of circadian rhythms. The protein encodes a transcription factor of the basic helix-loop-helix (bHLH) family and contains DNA binding histone acetyltransferase activity. The encoded protein forms a heterodimer with ARNTL (BMAL1) that binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Polymorphisms in this gene may be associated with behavioral changes in certain populations and with obesity and metabolic syndrome. Alternative splicing results in multiple transcript variants. [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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLOCK	NM_004898.4	MANE Select	c.793-1130T>C		intron	N/A	NP_004889.1	O15516
	CLOCK	NM_001267843.2		c.793-1130T>C		intron	N/A	NP_001254772.1	O15516

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLOCK	ENST00000513440.6	TSL:1 MANE Select	c.793-1130T>C		intron	N/A	ENSP00000426983.1	O15516
	CLOCK	ENST00000309964.8	TSL:1	c.793-1130T>C		intron	N/A	ENSP00000308741.4	O15516
	CLOCK	ENST00000381322.5	TSL:1	c.793-1130T>C		intron	N/A	ENSP00000370723.1	O15516

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58797 AN: 151828 Hom.: 11683 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.387 AC: 58848 AN: 151946 Hom.: 11698 Cov.: 31 AF XY: 0.388 AC XY: 28798 AN XY: 74258

African (AFR) AF: 0.378 AC: 15639 AN: 41398

American (AMR) AF: 0.336 AC: 5127 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1433 AN: 3468

East Asian (EAS) AF: 0.103 AC: 535 AN: 5190

South Asian (SAS) AF: 0.433 AC: 2081 AN: 4808

European-Finnish (FIN) AF: 0.455 AC: 4798 AN: 10550

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28009 AN: 67956

Other (OTH) AF: 0.384 AC: 807 AN: 2104

Alfa AF: 0.390 Hom.: 18278

Bravo AF: 0.371

Asia WGS AF: 0.311 AC: 1081 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	7.1
DANN	Benign	0.83
PhyloP100		0.60
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: rs11932595; hg19: chr4-56323597;