Variant 1-156669792-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000368223.4(NES):c.4396A>G(p.Ser1466Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,613,966 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 37 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 35 hom. )

Consequence

NES
ENST00000368223.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.715

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=0.0026652515).

BP6

Variant 1-156669792-T-C is Benign according to our data. Variant chr1-156669792-T-C is described in ClinVar as [Benign]. Clinvar id is 782391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1788/152144) while in subpopulation AFR AF= 0.0414 (1716/41496). AF 95% confidence interval is 0.0397. There are 37 homozygotes in gnomad4. There are 867 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NES	NM_006617.2 linkuse as main transcript	c.4396A>G	p.Ser1466Gly	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.4396A>G	p.Ser1466Gly	missense_variant	4/4	1	NM_006617.2	ENSP00000357206	P1

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1782

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00329

AC:

826

AN:

251118

Hom.:

AF XY:

0.00231

AC XY:

314

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0448

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00125

AC:

1825

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

760

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0430

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.0118

AC:

1788

AN:

152144

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

867

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0414

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.0135

ESP6500AA

AF:

0.0377

AC:

166

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00403

AC:

489

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.1

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Benign

0.17

Polyphen

0.041

Vest4

0.23

MVP

0.66

MPC

0.090

ClinPred

0.016

GERP RS

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.016

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