Variant 2-231456087-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005381.3(NCL):c.1755A>G(p.Glu585Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,614,182 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 22 hom., cov: 33)

Exomes 𝑓: 0.00093 ( 19 hom. )

Consequence

NCL
NM_005381.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.245

Variant links:

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 links:

NCL (HGNC:):

NCL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 2-231456087-T-C is Benign according to our data. Variant chr2-231456087-T-C is described in ClinVar as [Benign]. Clinvar id is 783994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.245 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00917 (1397/152296) while in subpopulation AFR AF= 0.0322 (1339/41550). AF 95% confidence interval is 0.0308. There are 22 homozygotes in gnomad4. There are 654 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1397 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCL	NM_005381.3 linkuse as main transcript	c.1755A>G	p.Glu585Glu	synonymous_variant	12/14	ENST00000322723.9	NP_005372.2	P19338B3KM80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCL	ENST00000322723.9 linkuse as main transcript	c.1755A>G	p.Glu585Glu	synonymous_variant	12/14	2	NM_005381.3	ENSP00000318195.4		P19338

Frequencies

GnomAD3 genomes

AF:

0.00915

AC:

1393

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00217

AC:

545

AN:

251480

Hom.:

AF XY:

0.00161

AC XY:

219

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0296

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000930

AC:

1359

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000843

AC XY:

613

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0332

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00917

AC:

1397

AN:

152296

Hom.:

Cov.:

AF XY:

0.00878

AC XY:

654

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0322

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00388

Hom.:

Bravo

AF:

0.0100

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.3

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over