chr4-139018499-G-A

Variant names:

• chr4-139018499-G-A
• rs938836
• NM_012118.4:c.190+2328G>A

Variant summary

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

The NM_012118.4(NOCT):​c.190+2328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,050 control chromosomes in the GnomAD database, including 13,480 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 0.41 (13480 hom., cov: 33)
• Consequence: NOCT NM_012118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOCT	NM_012118.4	c.190+2328G>A		intron_variant	Intron 1 of 2	ENST00000280614.4	NP_036250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOCT	ENST00000280614.4	c.190+2328G>A		intron_variant	Intron 1 of 2	1	NM_012118.4	ENSP00000280614.2
NOCT	ENST00000630479.1	n.190+2328G>A		intron_variant	Intron 1 of 2	5		ENSP00000486546.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62735 AN: 151932 Hom.: 13487 Cov.: 33

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.413 AC: 62732 AN: 152050 Hom.: 13480 Cov.: 33 AF XY: 0.413 AC XY: 30661 AN XY: 74328

African (AFR) AF: 0.357 AC: 14793 AN: 41472

American (AMR) AF: 0.335 AC: 5120 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1446 AN: 3472

East Asian (EAS) AF: 0.129 AC: 667 AN: 5182

South Asian (SAS) AF: 0.469 AC: 2260 AN: 4822

European-Finnish (FIN) AF: 0.483 AC: 5104 AN: 10558

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32008 AN: 67968

Other (OTH) AF: 0.424 AC: 893 AN: 2108

Alfa AF: 0.444 Hom.: 3482

Bravo AF: 0.396

Asia WGS AF: 0.317 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.4
DANN	Benign	0.75
PhyloP100		-0.56
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: rs938836; hg19: chr4-139939653;