Variant 1-71592927-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_173808.3(NEGR1):c.830G>A(p.Ser277Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000157 in 1,611,968 control chromosomes in the GnomAD database, including 1 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00085 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

NEGR1
NM_173808.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.86

Variant links:

Genes affected

NEGR1 (HGNC:17302): (neuronal growth regulator 1) Predicted to act upstream of or within several processes, including feeding behavior; locomotory behavior; and positive regulation of neuron projection development. Predicted to be located in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

NEGR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007464379).

BP6

Variant 1-71592927-C-T is Benign according to our data. Variant chr1-71592927-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 724718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEGR1	NM_173808.3 linkuse as main transcript	c.830G>A	p.Ser277Asn	missense_variant	6/7	ENST00000357731.10
NEGR1	XM_011541200.4 linkuse as main transcript	c.830G>A	p.Ser277Asn	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10 linkuse as main transcript	c.830G>A	p.Ser277Asn	missense_variant	6/7	1	NM_173808.3	P1	Q7Z3B1-1
NEGR1	ENST00000306821.3 linkuse as main transcript	c.446G>A	p.Ser149Asn	missense_variant	6/7	1			Q7Z3B1-2

Frequencies

GnomAD3 genomes

AF:

0.000848

AC:

129

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00297

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000199

AC:

AN:

251188

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.00289

Gnomad AMR exome

AF:

0.0000869

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000849

AC:

124

AN:

1459708

Hom.:

Cov.:

AF XY:

0.0000661

AC XY:

AN XY:

726286

show subpopulations

Gnomad4 AFR exome

AF:

0.00332

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000847

AC:

129

AN:

152260

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00296

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000119

Hom.:

Bravo

AF:

0.000831

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000231

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

NEGR1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

0.029

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.0075

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.86

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.043

Sift

Benign

0.41

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0010

B;.

Vest4

0.17

MVP

0.16

MPC

0.40

ClinPred

0.023

GERP RS

4.9

Varity_R

0.25

gMVP

0.49

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