rs989488

Variant names:

• chr18-33874180-T-C
• rs989488
• NM_003787.5:c.1723+9064A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003787.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL4	NM_003787.5	MANE Select	c.1723+9064A>G		intron	N/A	NP_003778.2	O94818-1
	NOL4	NM_001384467.1		c.1792+9064A>G		intron	N/A	NP_001371396.1
	NOL4	NM_001384468.1		c.1600+9064A>G		intron	N/A	NP_001371397.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL4	ENST00000261592.10	TSL:1 MANE Select	c.1723+9064A>G		intron	N/A	ENSP00000261592.4	O94818-1
	NOL4	ENST00000589544.5	TSL:1	c.1417+9064A>G		intron	N/A	ENSP00000465450.1	O94818-2
	NOL4	ENST00000538587.5	TSL:2	c.1501+9064A>G		intron	N/A	ENSP00000443472.1	O94818-3

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

African (AFR) AF: 0.110 AC: 4549 AN: 41438

American (AMR) AF: 0.285 AC: 4330 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3468

East Asian (EAS) AF: 0.387 AC: 1979 AN: 5118

South Asian (SAS) AF: 0.194 AC: 936 AN: 4820

European-Finnish (FIN) AF: 0.305 AC: 3208 AN: 10532

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13996 AN: 67810

Other (OTH) AF: 0.191 AC: 401 AN: 2102

Alfa AF: 0.206 Hom.: 14420

Bravo AF: 0.196

Asia WGS AF: 0.287 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.55
PhyloP100		0.61
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: rs989488; hg19: chr18-31454144;