rs3805213

Variant names:

• chr4-139044570-C-T
• rs3805213
• NM_012118.4:c.461-69C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NOCT	NM_012118.4	c.461-69C>T		intron_variant	Intron 2 of 2	ENST00000280614.4	NP_036250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOCT	ENST00000280614.4	c.461-69C>T		intron_variant	Intron 2 of 2	1	NM_012118.4	ENSP00000280614.2
NOCT	ENST00000515616.1	n.273-69C>T		intron_variant	Intron 1 of 1	1
ELF2	ENST00000515489.1	n.272+15754G>A		intron_variant	Intron 1 of 1	2
NOCT	ENST00000630479.1	n.*504+679C>T		intron_variant	Intron 2 of 2	5		ENSP00000486546.1

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

African (AFR) AF: 0.240 AC: 4977 AN: 20734

American (AMR) AF: 0.123 AC: 4016 AN: 32680

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 3527 AN: 17674

East Asian (EAS) AF: 0.0417 AC: 1530 AN: 36682

South Asian (SAS) AF: 0.144 AC: 8750 AN: 60840

European-Finnish (FIN) AF: 0.245 AC: 11784 AN: 48006

Middle Eastern (MID) AF: 0.245 AC: 819 AN: 3344

European-Non Finnish (NFE) AF: 0.249 AC: 144417 AN: 580014

Other (OTH) AF: 0.219 AC: 8584 AN: 39242

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

African (AFR) AF: 0.239 AC: 9920 AN: 41478

American (AMR) AF: 0.176 AC: 2698 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 703 AN: 3472

East Asian (EAS) AF: 0.0530 AC: 275 AN: 5186

South Asian (SAS) AF: 0.138 AC: 664 AN: 4816

European-Finnish (FIN) AF: 0.253 AC: 2668 AN: 10554

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16833 AN: 67976

Other (OTH) AF: 0.237 AC: 500 AN: 2108

Alfa AF: 0.242 Hom.: 735

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
PhyloP100		0.092
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: rs3805213; hg19: chr4-139965724;