Genetic Variant NES:p.Gly1407Arg (chr1-156669969-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006617.2(NES):c.4219G>A(p.Gly1407Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,613,802 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 25 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 24 hom. )

Consequence

NES
NM_006617.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.248

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002946794).

BP6

Variant 1-156669969-C-T is Benign according to our data. Variant chr1-156669969-C-T is described in ClinVar as Benign. ClinVar VariationId is 782392.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 = 0.00992 (1510/152220) while in subpopulation AFR AF = 0.035 (1451/41514). AF 95% confidence interval is 0.0335. There are 25 homozygotes in GnomAd4. There are 733 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006617.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NES	NM_006617.2	MANE Select	c.4219G>A	p.Gly1407Arg	missense	Exon 4 of 4	NP_006608.1	P48681

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NES	ENST00000368223.4	TSL:1 MANE Select	c.4219G>A	p.Gly1407Arg	missense	Exon 4 of 4	ENSP00000357206.3	P48681
	NES	ENST00000867897.1		c.3253G>A	p.Gly1085Arg	missense	Exon 4 of 4	ENSP00000537956.1

Frequencies

GnomAD3 genomes

AF:

0.00989

AC:

1505

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

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:

0.00479

GnomAD2 exomes

AF:

0.00265

AC:

658

AN:

248556

AF XY:

0.00196

show subpopulations

Gnomad AFR exome

AF:

0.0367

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000804

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00103

AC:

1509

AN:

1461582

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

625

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.0349

AC:

1167

AN:

33480

American (AMR)

AF:

0.00266

AC:

119

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000927

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53224

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

1111932

Other (OTH)

AF:

0.00253

AC:

153

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

198

298

397

496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00992

AC:

1510

AN:

152220

Hom.:

Cov.:

AF XY:

0.00985

AC XY:

733

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0350

AC:

1451

AN:

41514

American (AMR)

AF:

0.00281

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67998

Other (OTH)

AF:

0.00474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

144

217

289

361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00391

Hom.:

Bravo

AF:

0.0112

ESP6500AA

AF:

0.0304

AC:

134

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00330

AC:

401

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.50

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.4

PhyloP100

0.25

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.11

Sift

Benign

0.17

Sift4G

Benign

0.29

Polyphen

0.020

Vest4

0.16

MutPred

0.15

Loss of glycosylation at S1409 (P = 0.0819)

MVP

0.74

MPC

0.099

ClinPred

0.0092

GERP RS

0.96

Varity_R

0.097

gMVP

0.0090

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over