Genetic Variant NRN1:p.Gly7Ser (chr6-6006731-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016588.3(NRN1):c.19G>A(p.Gly7Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000591 in 1,614,120 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G7R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 4 hom. )

Consequence

NRN1
NM_016588.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.97

Publications

2 publications found

Variant links:

Genes affected

NRN1 (HGNC:17972): (neuritin 1) This gene encodes a member of the neuritin family, and is expressed in postmitotic-differentiating neurons of the developmental nervous system and neuronal structures associated with plasticity in the adult. The expression of this gene can be induced by neural activity and neurotrophins. The encoded protein contains a consensus cleavage signal found in glycosylphoshatidylinositol (GPI)-anchored proteins. The encoded protein promotes neurite outgrowth and arborization, suggesting its role in promoting neuritogenesis. Overexpression of the encoded protein may be associated with astrocytoma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

NRN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008473337).

BP6

Variant 6-6006731-C-T is Benign according to our data. Variant chr6-6006731-C-T is described in ClinVar as Benign. ClinVar VariationId is 712450.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016588.3. 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
	NRN1	NM_016588.3	MANE Select	c.19G>A	p.Gly7Ser	missense	Exon 1 of 3	NP_057672.1	Q9NPD7
	NRN1	NM_001278710.2		c.19G>A	p.Gly7Ser	missense	Exon 2 of 4	NP_001265639.1	Q9NPD7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NRN1	ENST00000244766.7	TSL:1 MANE Select	c.19G>A	p.Gly7Ser	missense	Exon 1 of 3	ENSP00000244766.2	Q9NPD7
NRN1	ENST00000616243.1	TSL:4	c.19G>A	p.Gly7Ser	missense	Exon 2 of 4	ENSP00000484055.1	Q9NPD7
NRN1	ENST00000889857.1		c.19G>A	p.Gly7Ser	missense	Exon 2 of 4	ENSP00000559916.1

Frequencies

GnomAD3 genomes

AF:

0.00317

AC:

482

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000775

AC:

195

AN:

251480

AF XY:

0.000522

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000323

AC:

472

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

211

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.0111

AC:

372

AN:

33470

American (AMR)

AF:

0.000514

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1111960

Other (OTH)

AF:

0.000795

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00316

AC:

482

AN:

152302

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

221

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0111

AC:

461

AN:

41556

American (AMR)

AF:

0.000915

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68022

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00147

Hom.:

Bravo

AF:

0.00362

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000873

AC:

106

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0085

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.81

PhyloP100

6.0

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.4

REVEL

Benign

0.16

Sift

Benign

0.28

Sift4G

Benign

0.33

Polyphen

0.99

Vest4

0.66

MVP

0.12

MPC

0.73

ClinPred

0.045

GERP RS

4.1

PromoterAI

-0.084

Neutral

(source)

Varity_R

0.18

Mutation Taster

=58/42

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