Variant rs3748570 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006617.2(NES):c.3824C>T(p.Pro1275Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,607,838 control chromosomes in the GnomAD database, including 345,128 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.67 ( 34899 hom., cov: 32)

Exomes 𝑓: 0.65 ( 310229 hom. )

Consequence

NES
NM_006617.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

NES (HGNC:7756): (nestin) This gene encodes a member of the intermediate filament protein family and is expressed primarily in nerve cells. [provided by RefSeq, Sep 2011]

NES links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.881236E-7).

BP6

Variant 1-156670364-G-A is Benign according to our data. Variant chr1-156670364-G-A is described in ClinVar as [Benign]. Clinvar id is 1238056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NES	NM_006617.2 linkuse as main transcript	c.3824C>T	p.Pro1275Leu	missense_variant	4/4	ENST00000368223.4	NP_006608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NES	ENST00000368223.4 linkuse as main transcript	c.3824C>T	p.Pro1275Leu	missense_variant	4/4	1	NM_006617.2	ENSP00000357206	P1

Frequencies

GnomAD3 genomes

AF:

0.675

AC:

102537

AN:

151902

Hom.:

34873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.696

Gnomad AMI

AF:

0.571

Gnomad AMR

AF:

0.724

Gnomad ASJ

AF:

0.709

Gnomad EAS

AF:

0.861

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.653

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.642

Gnomad OTH

AF:

0.692

GnomAD3 exomes

AF:

0.677

AC:

166801

AN:

246448

Hom.:

56966

AF XY:

0.670

AC XY:

89133

AN XY:

133116

show subpopulations

Gnomad AFR exome

AF:

0.693

Gnomad AMR exome

AF:

0.714

Gnomad ASJ exome

AF:

0.711

Gnomad EAS exome

AF:

0.865

Gnomad SAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.663

Gnomad NFE exome

AF:

0.645

Gnomad OTH exome

AF:

0.680

GnomAD4 exome

AF:

0.651

AC:

948281

AN:

1455820

Hom.:

310229

Cov.:

AF XY:

0.650

AC XY:

470479

AN XY:

723766

show subpopulations

Gnomad4 AFR exome

AF:

0.694

Gnomad4 AMR exome

AF:

0.718

Gnomad4 ASJ exome

AF:

0.710

Gnomad4 EAS exome

AF:

0.809

Gnomad4 SAS exome

AF:

0.626

Gnomad4 FIN exome

AF:

0.662

Gnomad4 NFE exome

AF:

0.641

Gnomad4 OTH exome

AF:

0.674

GnomAD4 genome

AF:

0.675

AC:

102607

AN:

152018

Hom.:

34899

Cov.:

AF XY:

0.678

AC XY:

50404

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.695

Gnomad4 AMR

AF:

0.725

Gnomad4 ASJ

AF:

0.709

Gnomad4 EAS

AF:

0.861

Gnomad4 SAS

AF:

0.639

Gnomad4 FIN

AF:

0.653

Gnomad4 NFE

AF:

0.642

Gnomad4 OTH

AF:

0.695

Alfa

AF:

0.659

Hom.:

72421

Bravo

AF:

0.683

TwinsUK

AF:

0.628

AC:

2330

ALSPAC

AF:

0.635

AC:

2446

ESP6500AA

AF:

0.693

AC:

3055

ESP6500EA

AF:

0.643

AC:

5527

ExAC

AF:

0.671

AC:

81471

Asia WGS

AF:

0.775

AC:

2688

AN:

3476

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	GeneDx	Feb 24, 2021	This variant is associated with the following publications: (PMID: 18724036) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.094

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.34

MetaRNN

Benign

5.9e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

3.3

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.054

MPC

0.057

ClinPred

0.0052

GERP RS

5.0

Varity_R

0.040

gMVP

0.017

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