9-92321784-T-C

Variant names:

• chr9-92321784-T-C
• rs2274967
• NM_017948.6:c.203-38A>G

Variant summary

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

The NM_017948.6(NOL8):​c.203-38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 990,684 control chromosomes in the GnomAD database, including 1,428 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 0.061 (405 hom., cov: 33)
  • Exomes 𝑓: 0.044 (1023 hom.)
• Consequence: NOL8 NM_017948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 6 publications found

Genes affected

NOL8 (HGNC:23387): (nucleolar protein 8) NOL8 binds Ras-related GTP-binding proteins (see MIM 608267) and plays a role in cell growth (Sekiguchi et al., 2004 [PubMed 14660641]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL8	NM_017948.6	c.203-38A>G		intron_variant	Intron 3 of 16	ENST00000442668.7	NP_060418.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOL8	ENST00000442668.7	c.203-38A>G		intron_variant	Intron 3 of 16	1	NM_017948.6	ENSP00000401177.2
NOL8	ENST00000542053.5	c.-2-38A>G		intron_variant	Intron 2 of 15	5		ENSP00000440709.1
NOL8	ENST00000432670.6	c.203-38A>G		intron_variant	Intron 3 of 12	5		ENSP00000414112.2
NOL8	ENST00000421075.6	c.203-38A>G		intron_variant	Intron 3 of 6	5		ENSP00000390143.2
NOL8	ENST00000360868.7	n.*58-38A>G		intron_variant	Intron 3 of 16	2		ENSP00000354115.3
NOL8	ENST00000434228.5	n.*58-38A>G		intron_variant	Intron 4 of 12	2		ENSP00000415750.1

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9316 AN: 152202 Hom.: 406 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.0521

GnomAD2 exomes AF: 0.0471 AC: 4478 AN: 95128 AF XY: 0.0474

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.0321

Gnomad ASJ exome AF: 0.0627

Gnomad EAS exome AF: 0.0489

Gnomad FIN exome AF: 0.0188

Gnomad NFE exome AF: 0.0418

Gnomad OTH exome AF: 0.0402

GnomAD4 exome AF: 0.0439 AC: 36797 AN: 838364 Hom.: 1023 Cov.: 11 AF XY: 0.0449 AC XY: 19344 AN XY: 431062

African (AFR) AF: 0.118 AC: 2105 AN: 17838

American (AMR) AF: 0.0340 AC: 538 AN: 15818

Ashkenazi Jewish (ASJ) AF: 0.0639 AC: 1225 AN: 19178

East Asian (EAS) AF: 0.0488 AC: 1489 AN: 30488

South Asian (SAS) AF: 0.0696 AC: 3949 AN: 56724

European-Finnish (FIN) AF: 0.0203 AC: 929 AN: 45662

Middle Eastern (MID) AF: 0.0309 AC: 137 AN: 4428

European-Non Finnish (NFE) AF: 0.0404 AC: 24616 AN: 609998

Other (OTH) AF: 0.0473 AC: 1809 AN: 38230

GnomAD4 genome AF: 0.0612 AC: 9327 AN: 152320 Hom.: 405 Cov.: 33 AF XY: 0.0593 AC XY: 4414 AN XY: 74488

African (AFR) AF: 0.113 AC: 4683 AN: 41558

American (AMR) AF: 0.0399 AC: 610 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3470

East Asian (EAS) AF: 0.0397 AC: 206 AN: 5188

South Asian (SAS) AF: 0.0795 AC: 384 AN: 4828

European-Finnish (FIN) AF: 0.0187 AC: 199 AN: 10618

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0417 AC: 2835 AN: 68034

Other (OTH) AF: 0.0535 AC: 113 AN: 2114

Alfa AF: 0.0517 Hom.: 56

Bravo AF: 0.0645

Asia WGS AF: 0.0900 AC: 314 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.6
DANN	Benign	0.62
PhyloP100		-0.32
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: rs2274967; hg19: chr9-95084066;