4-139025494-A-G

Position:

• chr4-139025494-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOCT	NM_012118.4	c.190+9323A>G		intron_variant		ENST00000280614.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOCT	ENST00000280614.4	c.190+9323A>G		intron_variant		1	NM_012118.4	P1
NOCT	ENST00000630479.1	c.190+9323A>G		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.297

Alfa AF: 0.272 Hom.: 2086

Bravo AF: 0.288

Asia WGS AF: 0.259 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.39

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: rs17050680; hg19: chr4-139946648;