4-139025494-A-G

Variant names:

• chr4-139025494-A-G
• rs17050680
• NM_012118.4:c.190+9323A>G

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+9323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,968 control chromosomes in the GnomAD database, including 6,520 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 0.29 (6520 hom., cov: 32)
• Consequence: NOCT NM_012118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012118.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOCT	NM_012118.4	MANE Select	c.190+9323A>G		intron	N/A	NP_036250.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOCT	ENST00000280614.4	TSL:1 MANE Select	c.190+9323A>G		intron	N/A	ENSP00000280614.2
	NOCT	ENST00000630479.1	TSL:5	n.190+9323A>G		intron	N/A	ENSP00000486546.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43993 AN: 151850 Hom.: 6499 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.290 AC: 44059 AN: 151968 Hom.: 6520 Cov.: 32 AF XY: 0.285 AC XY: 21193 AN XY: 74264

African (AFR) AF: 0.324 AC: 13435 AN: 41434

American (AMR) AF: 0.211 AC: 3225 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1126 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1093 AN: 5166

South Asian (SAS) AF: 0.339 AC: 1638 AN: 4826

European-Finnish (FIN) AF: 0.240 AC: 2525 AN: 10530

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.293 AC: 19948 AN: 67970

Other (OTH) AF: 0.297 AC: 626 AN: 2110

Alfa AF: 0.276 Hom.: 3581

Bravo AF: 0.288

Asia WGS AF: 0.259 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.39
PhyloP100		-1.2
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: rs17050680; hg19: chr4-139946648;