Variant 2-231456731-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_005381.3(NCL):c.1605C>T(p.Asp535Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,614,076 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 11 hom. )

Consequence

NCL
NM_005381.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.58

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 2-231456731-G-A is Benign according to our data. Variant chr2-231456731-G-A is described in ClinVar as [Benign]. Clinvar id is 712368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.58 with no splicing effect.

BS2

High AC in GnomAd4 at 846 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCL	NM_005381.3 linkuse as main transcript	c.1605C>T	p.Asp535Asp	synonymous_variant	11/14	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.1605C>T	p.Asp535Asp	synonymous_variant	11/14	2	NM_005381.3	ENSP00000318195.4		P19338

Frequencies

GnomAD3 genomes

AF:

0.00555

AC:

844

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00623

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00261

AC:

657

AN:

251438

Hom.:

AF XY:

0.00224

AC XY:

304

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0140

Gnomad AMR exome

AF:

0.00544

Gnomad ASJ exome

AF:

0.00317

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00141

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00159

AC:

2329

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

1133

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0150

Gnomad4 AMR exome

AF:

0.00575

Gnomad4 ASJ exome

AF:

0.00352

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.00387

GnomAD4 genome

AF:

0.00556

AC:

846

AN:

152204

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

393

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.00622

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00355

Hom.:

Bravo

AF:

0.00640

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00229

EpiControl

AF:

0.00184

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	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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