2-231461706-C-T

Position:

• chr2-231461706-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005381.3(NCL):​c.447G>A​(p.Glu149Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,562 control chromosomes in the GnomAD database, including 49,426 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 0.29 (7875 hom., cov: 33)
  • Exomes 𝑓: 0.22 (41551 hom.)
• Consequence: NCL NM_005381.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.38

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]

NCL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-6.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCL	NM_005381.3	c.447G>A	p.Glu149Glu	synonymous_variant	3/14	ENST00000322723.9	NP_005372.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCL	ENST00000322723.9	c.447G>A	p.Glu149Glu	synonymous_variant	3/14	2	NM_005381.3	ENSP00000318195.4

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44682 AN: 151976 Hom.: 7860 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.289

GnomAD3 exomes AF: 0.287 AC: 71963 AN: 250796 Hom.: 12291 AF XY: 0.282 AC XY: 38309 AN XY: 135610

Gnomad AFR exome AF: 0.460

Gnomad AMR exome AF: 0.337

Gnomad ASJ exome AF: 0.213

Gnomad EAS exome AF: 0.583

Gnomad SAS exome AF: 0.389

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.252

GnomAD4 exome AF: 0.216 AC: 315850 AN: 1461468 Hom.: 41551 Cov.: 34 AF XY: 0.221 AC XY: 160369 AN XY: 727068

Gnomad4 AFR exome AF: 0.457

Gnomad4 AMR exome AF: 0.332

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.605

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.294 AC: 44732 AN: 152094 Hom.: 7875 Cov.: 33 AF XY: 0.298 AC XY: 22181 AN XY: 74348

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.294

Alfa AF: 0.211 Hom.: 6422

Bravo AF: 0.303

Asia WGS AF: 0.516 AC: 1789 AN: 3478

EpiCase AF: 0.191

EpiControl AF: 0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.031
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs1131171; hg19: chr2-232326417; COSMIC: COSV59545966; COSMIC: COSV59545966;