rs4864548

Variant names:

• chr4-55547636-G-A
• rs4864548
• ENST00000609234.1:n.525G>A

Variant summary

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

The ENST00000726601.1(ENSG00000272969):​n.232G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,104 control chromosomes in the GnomAD database, including 9,396 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 0.34 (9396 hom., cov: 32)
  • Exomes 𝑓: 0.30 (0 hom.)
• Consequence: ENSG00000272969 ENST00000726601.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 60 publications found

Genes affected

ENSG00000272969 (HGNC:58790):

LOC124900704 (HGNC:):

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000726601.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000272969	ENST00000609234.1	TSL:6	n.525G>A		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000272969	ENST00000726601.1		n.232G>A		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000272969	ENST00000726602.1		n.372G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51405 AN: 151976 Hom.: 9387 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.300 AC: 3 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.338 AC: 51414 AN: 152094 Hom.: 9396 Cov.: 32 AF XY: 0.346 AC XY: 25691 AN XY: 74332

African (AFR) AF: 0.198 AC: 8218 AN: 41494

American (AMR) AF: 0.438 AC: 6704 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3468

East Asian (EAS) AF: 0.584 AC: 3013 AN: 5156

South Asian (SAS) AF: 0.440 AC: 2117 AN: 4814

European-Finnish (FIN) AF: 0.395 AC: 4181 AN: 10576

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24633 AN: 67976

Other (OTH) AF: 0.342 AC: 722 AN: 2112

Alfa AF: 0.351 Hom.: 23444

Bravo AF: 0.337

Asia WGS AF: 0.475 AC: 1652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.53
PhyloP100		0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4864548; hg19: chr4-56413803;