NM_005381.3:c.1448-121G>A

Variant names:

• chr2-231457245-C-T
• rs7598759
• NM_005381.3:c.1448-121G>A

Variant summary

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

The NM_005381.3(NCL):​c.1448-121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,348,226 control chromosomes in the GnomAD database, including 125,039 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 0.46 (16303 hom., cov: 32)
  • Exomes 𝑓: 0.42 (108736 hom.)
• Consequence: NCL NM_005381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 23 publications found

Genes affected

NCL (HGNC:7667): (nucleolin) Nucleolin (NCL), a eukaryotic nucleolar phosphoprotein, is involved in the synthesis and maturation of ribosomes. It is located mainly in dense fibrillar regions of the nucleolus. Human NCL gene consists of 14 exons with 13 introns and spans approximately 11kb. The intron 11 of the NCL gene encodes a small nucleolar RNA, termed U20. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005381.3. 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
	NCL	NM_005381.3	MANE Select	c.1448-121G>A		intron	N/A	NP_005372.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCL	ENST00000322723.9	TSL:2 MANE Select	c.1448-121G>A		intron	N/A	ENSP00000318195.4
	NCL	ENST00000466274.1	TSL:2	n.166G>A		non_coding_transcript_exon	Exon 1 of 3
	NCL	ENST00000676798.1		n.2010G>A		non_coding_transcript_exon	Exon 9 of 12

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69884 AN: 151920 Hom.: 16290 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.450

GnomAD2 exomes AF: 0.447 AC: 99427 AN: 222642 AF XY: 0.444

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.456

Gnomad ASJ exome AF: 0.529

Gnomad EAS exome AF: 0.519

Gnomad FIN exome AF: 0.413

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.423 AC: 505572 AN: 1196188 Hom.: 108736 Cov.: 16 AF XY: 0.423 AC XY: 256637 AN XY: 606274

African (AFR) AF: 0.542 AC: 15300 AN: 28218

American (AMR) AF: 0.453 AC: 18627 AN: 41118

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 12627 AN: 24158

East Asian (EAS) AF: 0.568 AC: 21688 AN: 38156

South Asian (SAS) AF: 0.411 AC: 32381 AN: 78870

European-Finnish (FIN) AF: 0.420 AC: 21937 AN: 52200

Middle Eastern (MID) AF: 0.412 AC: 2167 AN: 5266

European-Non Finnish (NFE) AF: 0.409 AC: 358654 AN: 876708

Other (OTH) AF: 0.431 AC: 22191 AN: 51494

GnomAD4 genome AF: 0.460 AC: 69941 AN: 152038 Hom.: 16303 Cov.: 32 AF XY: 0.459 AC XY: 34083 AN XY: 74306

African (AFR) AF: 0.548 AC: 22708 AN: 41434

American (AMR) AF: 0.438 AC: 6692 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1832 AN: 3470

East Asian (EAS) AF: 0.518 AC: 2685 AN: 5180

South Asian (SAS) AF: 0.414 AC: 1998 AN: 4826

European-Finnish (FIN) AF: 0.397 AC: 4195 AN: 10568

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28357 AN: 67968

Other (OTH) AF: 0.449 AC: 946 AN: 2106

Alfa AF: 0.438 Hom.: 35155

Bravo AF: 0.467

Asia WGS AF: 0.461 AC: 1601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.45
DANN	Benign	0.60
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs7598759; hg19: chr2-232321956; COSMIC: COSV107379527; COSMIC: COSV107379527;