rs989488

Positions:

• chr18-33874180-T-C

Variant summary

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

The NM_003787.5(NOL4):​c.1723+9064A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,662 control chromosomes in the GnomAD database, including 3,497 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 0.20 (3497 hom., cov: 32)
• Consequence: NOL4 NM_003787.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610

Genes affected

NOL4 (HGNC:7870): (nucleolar protein 4) Predicted to enable RNA binding activity. Predicted to be located in nucleolus. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOL4	NM_003787.5	c.1723+9064A>G		intron_variant		ENST00000261592.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOL4	ENST00000261592.10	c.1723+9064A>G		intron_variant		1	NM_003787.5	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30374 AN: 151544 Hom.: 3481 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.201 AC: 30432 AN: 151662 Hom.: 3497 Cov.: 32 AF XY: 0.207 AC XY: 15314 AN XY: 74056

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.191

Alfa AF: 0.206 Hom.: 6933

Bravo AF: 0.196

Asia WGS AF: 0.287 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.55

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: rs989488; hg19: chr18-31454144;