rs1112828

Positions:

• chr4-139035816-G-T

Variant summary

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

The NM_012118.4(NOCT):​c.191-7258G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,928 control chromosomes in the GnomAD database, including 4,935 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 0.22 (4935 hom., cov: 32)
• Consequence: NOCT NM_012118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOCT	NM_012118.4	c.191-7258G>T		intron_variant		ENST00000280614.4	NP_036250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOCT	ENST00000280614.4	c.191-7258G>T		intron_variant		1	NM_012118.4	ENSP00000280614	P1
NOCT	ENST00000630479.1	c.191-7258G>T		intron_variant, NMD_transcript_variant		5		ENSP00000486546
ELF2	ENST00000515489.1	n.273-7467C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33743 AN: 151810 Hom.: 4918 Cov.: 32

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.222 AC: 33770 AN: 151928 Hom.: 4935 Cov.: 32 AF XY: 0.230 AC XY: 17066 AN XY: 74204

Gnomad4 AFR AF: 0.0921

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.221

Alfa AF: 0.229 Hom.: 7833

Bravo AF: 0.230

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.99
DANN	Benign	0.84

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: rs1112828; hg19: chr4-139956970;