2-10575262-T-C

Variant names:

• chr2-10575262-T-C
• rs6757809
• NM_024894.4:c.1947+2374A>G

Variant summary

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

The ENST00000381685.10(NOL10):​c.1947+2374A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,170 control chromosomes in the GnomAD database, including 6,508 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 0.25 (6508 hom., cov: 33)
• Consequence: NOL10 ENST00000381685.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.28
• Publications: 2 publications found

Genes affected

NOL10 (HGNC:25862): (nucleolar protein 10) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381685.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL10	NM_024894.4	MANE Select	c.1947+2374A>G		intron	N/A	NP_079170.2
	NOL10	NM_001261392.2		c.1869+2374A>G		intron	N/A	NP_001248321.1
	NOL10	NM_001261394.2		c.1797+2374A>G		intron	N/A	NP_001248323.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL10	ENST00000381685.10	TSL:1 MANE Select	c.1947+2374A>G		intron	N/A	ENSP00000371101.5
	NOL10	ENST00000695473.1		n.6137A>G		non_coding_transcript_exon	Exon 18 of 19
	NOL10	ENST00000695476.1		n.*3370A>G		non_coding_transcript_exon	Exon 20 of 20	ENSP00000511951.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37615 AN: 152052 Hom.: 6486 Cov.: 33

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.248 AC: 37685 AN: 152170 Hom.: 6508 Cov.: 33 AF XY: 0.255 AC XY: 18941 AN XY: 74412

African (AFR) AF: 0.451 AC: 18715 AN: 41496

American (AMR) AF: 0.313 AC: 4788 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 123 AN: 3470

East Asian (EAS) AF: 0.441 AC: 2278 AN: 5168

South Asian (SAS) AF: 0.116 AC: 561 AN: 4820

European-Finnish (FIN) AF: 0.235 AC: 2495 AN: 10596

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8087 AN: 68014

Other (OTH) AF: 0.206 AC: 436 AN: 2112

Alfa AF: 0.232 Hom.: 901

Bravo AF: 0.266

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.038
DANN	Benign	0.59
PhyloP100		-4.3
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: rs6757809; hg19: chr2-10715388;