chr18-34091638-G-A

Variant names:

• chr18-34091638-G-A
• rs12185438
• NM_003787.5:c.772+1827C>T

Variant summary

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

The NM_003787.5(NOL4):​c.772+1827C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,902 control chromosomes in the GnomAD database, including 17,991 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 0.48 (17991 hom., cov: 31)
• Consequence: NOL4 NM_003787.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL4	NM_003787.5	c.772+1827C>T		intron_variant	Intron 5 of 10	ENST00000261592.10	NP_003778.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOL4	ENST00000261592.10	c.772+1827C>T		intron_variant	Intron 5 of 10	1	NM_003787.5	ENSP00000261592.4

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73306 AN: 151784 Hom.: 17945 Cov.: 31

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.483 AC: 73414 AN: 151902 Hom.: 17991 Cov.: 31 AF XY: 0.485 AC XY: 36014 AN XY: 74242

African (AFR) AF: 0.522 AC: 21603 AN: 41422

American (AMR) AF: 0.529 AC: 8064 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1754 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2294 AN: 5148

South Asian (SAS) AF: 0.421 AC: 2029 AN: 4818

European-Finnish (FIN) AF: 0.508 AC: 5364 AN: 10558

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30683 AN: 67924

Other (OTH) AF: 0.474 AC: 1002 AN: 2112

Alfa AF: 0.460 Hom.: 43097

Bravo AF: 0.489

Asia WGS AF: 0.457 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		0.82
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: rs12185438; hg19: chr18-31671602;