NM_005381.3:c.*1148G>A

Variant names:

• chr2-231454043-C-T
• rs16828074
• NM_005381.3:c.*1148G>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.*1148G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 150,450 control chromosomes in the GnomAD database, including 206 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 0.026 (206 hom., cov: 32)
  • Exomes 𝑓: 0.033 (0 hom.)
• Consequence: NCL NM_005381.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCL	NM_005381.3	c.*1148G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000322723.9	NP_005372.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCL	ENST00000322723.9	c.*1148G>A		3_prime_UTR_variant	Exon 14 of 14	2	NM_005381.3	ENSP00000318195.4

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3816 AN: 150300 Hom.: 202 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.00378

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000786

Gnomad OTH AF: 0.0224

GnomAD4 exome AF: 0.0333 AC: 1 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.0417 AC XY: 1 AN XY: 24

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 28

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0255 AC: 3840 AN: 150420 Hom.: 206 Cov.: 32 AF XY: 0.0273 AC XY: 2004 AN XY: 73490

African (AFR) AF: 0.0382 AC: 1558 AN: 40820

American (AMR) AF: 0.0388 AC: 584 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.00378 AC: 13 AN: 3440

East Asian (EAS) AF: 0.206 AC: 1068 AN: 5174

South Asian (SAS) AF: 0.106 AC: 503 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000786 AC: 53 AN: 67446

Other (OTH) AF: 0.0293 AC: 61 AN: 2080

Alfa AF: 0.000357 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.38
PhyloP100		-0.36
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: rs16828074; hg19: chr2-232318754;