rs3805213

Positions:

• chr4-139044570-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012118.4(NOCT):​c.461-69C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 991,300 control chromosomes in the GnomAD database, including 26,405 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 0.23 (4057 hom., cov: 32)
  • Exomes 𝑓: 0.22 (22348 hom.)
• Consequence: NOCT NM_012118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

Genes affected

NOCT (HGNC:14254): (nocturnin) The protein encoded by this gene is highly similar to Nocturnin, a gene identified as a circadian clock regulated gene in Xenopus laevis. This protein and Nocturnin protein share similarity with the C-terminal domain of a yeast transcription factor, carbon catabolite repression 4 (CCR4). The mRNA abundance of a similar gene in mouse has been shown to exhibit circadian rhythmicity, which suggests a role for this protein in clock function or as a circadian clock effector. [provided by RefSeq, Jul 2008]

ELF2 (HGNC:3317): (E74 like ETS transcription factor 2) Enables DNA-binding transcription factor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription, DNA-templated; positive regulation of transcription, DNA-templated; and regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOCT	NM_012118.4	c.461-69C>T		intron_variant		ENST00000280614.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOCT	ENST00000280614.4	c.461-69C>T		intron_variant		1	NM_012118.4	P1
NOCT	ENST00000515616.1	n.273-69C>T		intron_variant, non_coding_transcript_variant		1
NOCT	ENST00000630479.1	c.*504+679C>T		intron_variant, NMD_transcript_variant		5
ELF2	ENST00000515489.1	n.272+15754G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34433 AN: 151964 Hom.: 4062 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0529

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.225 AC: 188404 AN: 839216 Hom.: 22348 AF XY: 0.223 AC XY: 96182 AN XY: 432214

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.0417

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.226 AC: 34436 AN: 152084 Hom.: 4057 Cov.: 32 AF XY: 0.222 AC XY: 16476 AN XY: 74332

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.0530

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.237

Alfa AF: 0.243 Hom.: 713

Bravo AF: 0.221

Asia WGS AF: 0.102 AC: 355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.67

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: rs3805213; hg19: chr4-139965724;