Variant 6-6006731-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★).

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

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 made for transcript

Verdict is Benign. Variant got -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 id is 712450.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRN1	NM_016588.3 linkuse as main transcript	c.19G>A	p.Gly7Ser	missense_variant	1/3	ENST00000244766.7	NP_057672.1	Q9NPD7
NRN1	NM_001278710.2 linkuse as main transcript	c.19G>A	p.Gly7Ser	missense_variant	2/4		NP_001265639.1	Q9NPD7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRN1	ENST00000244766.7 linkuse as main transcript	c.19G>A	p.Gly7Ser	missense_variant	1/3	1	NM_016588.3	ENSP00000244766.2		Q9NPD7
NRN1	ENST00000616243.1 linkuse as main transcript	c.19G>A	p.Gly7Ser	missense_variant	2/4	4		ENSP00000484055.1		Q9NPD7

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

GnomAD3 exomes

AF:

0.000775

AC:

195

AN:

251480

Hom.:

AF XY:

0.000522

AC XY:

AN XY:

135920

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 SAS exome

AF:

0.0000653

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

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.00316

AC:

482

AN:

152302

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

221

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0111

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00127

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

T;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.81

.;T

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.81

L;L

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.16

Sift

Benign

0.28

T;.

Sift4G

Benign

0.33

T;T

Polyphen

0.99

D;D

Vest4

0.66

MVP

0.12

MPC

0.73

ClinPred

0.045

GERP RS

4.1

Varity_R

0.18

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