dbSNP rs11582300: NES:p.Ser1409Ser (chr1-156669961-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006617.2(NES):c.4227C>T(p.Ser1409Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,612,362 control chromosomes in the GnomAD database, including 308,953 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 25720 hom., cov: 29)

Exomes 𝑓: 0.62 ( 283233 hom. )

Consequence

NES
NM_006617.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

21 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=-1.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NES	NM_006617.2 link	c.4227C>T	p.Ser1409Ser	synonymous_variant	Exon 4 of 4	ENST00000368223.4	NP_006608.1	P48681Q9H6U9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NES	ENST00000368223.4 link	c.4227C>T	p.Ser1409Ser	synonymous_variant	Exon 4 of 4	1	NM_006617.2	ENSP00000357206.3		P48681

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86295

AN:

150830

Hom.:

25705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.672

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.856

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.621

Gnomad OTH

AF:

0.612

GnomAD2 exomes

AF:

0.630

AC:

156379

AN:

248278

AF XY:

0.626

show subpopulations

Gnomad AFR exome

AF:

0.391

Gnomad AMR exome

AF:

0.685

Gnomad ASJ exome

AF:

0.637

Gnomad EAS exome

AF:

0.858

Gnomad FIN exome

AF:

0.609

Gnomad NFE exome

AF:

0.623

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.620

AC:

906039

AN:

1461414

Hom.:

283233

Cov.:

AF XY:

0.619

AC XY:

450016

AN XY:

727006

show subpopulations

African (AFR)

AF:

0.392

AC:

13118

AN:

33476

American (AMR)

AF:

0.685

AC:

30628

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.631

AC:

16498

AN:

26132

East Asian (EAS)

AF:

0.804

AC:

31926

AN:

39696

South Asian (SAS)

AF:

0.587

AC:

50632

AN:

86252

European-Finnish (FIN)

AF:

0.611

AC:

32497

AN:

53180

Middle Eastern (MID)

AF:

0.565

AC:

3261

AN:

5768

European-Non Finnish (NFE)

AF:

0.620

AC:

689447

AN:

1111816

Other (OTH)

AF:

0.630

AC:

38032

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

22107

44214

66320

88427

110534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18478

36956

55434

73912

92390

<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:

0.572

AC:

86332

AN:

150948

Hom.:

25720

Cov.:

AF XY:

0.577

AC XY:

42522

AN XY:

73716

show subpopulations

African (AFR)

AF:

0.399

AC:

16342

AN:

40938

American (AMR)

AF:

0.672

AC:

10224

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.627

AC:

2174

AN:

3468

East Asian (EAS)

AF:

0.857

AC:

4337

AN:

5062

South Asian (SAS)

AF:

0.594

AC:

2832

AN:

4770

European-Finnish (FIN)

AF:

0.606

AC:

6333

AN:

10444

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.621

AC:

42092

AN:

67748

Other (OTH)

AF:

0.613

AC:

1291

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1743

3486

5228

6971

8714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.595

Hom.:

21243

Bravo

AF:

0.570

Asia WGS

AF:

0.722

AC:

2507

AN:

3478

EpiCase

AF:

0.618

EpiControl

AF:

0.623

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.22

(source)

DANN

Benign

0.80

PhyloP100

-1.7

Mutation Taster

=99/1

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over