Variant 1-72282401-G-C 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_173808.3(NEGR1):c.94C>G(p.Leu32Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00792 in 1,613,908 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 5 hom., cov: 30)

Exomes 𝑓: 0.0081 ( 70 hom. )

Consequence

NEGR1
NM_173808.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.57

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052229166).

BP6

Variant 1-72282401-G-C is Benign according to our data. Variant chr1-72282401-G-C is described in ClinVar as [Benign]. Clinvar id is 713750.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NEGR1	NM_173808.3 linkuse as main transcript	c.94C>G	p.Leu32Val	missense_variant	1/7	ENST00000357731.10
NEGR1	XM_011541200.4 linkuse as main transcript	c.94C>G	p.Leu32Val	missense_variant	1/7
NEGR1	XM_011541201.4 linkuse as main transcript	c.94C>G	p.Leu32Val	missense_variant	1/5
NEGR1	XM_017000961.3 linkuse as main transcript	c.94C>G	p.Leu32Val	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10 linkuse as main transcript	c.94C>G	p.Leu32Val	missense_variant	1/7	1	NM_173808.3	P1	Q7Z3B1-1

Frequencies

GnomAD3 genomes

AF:

0.00602

AC:

914

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00564

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00595

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00944

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.00636

AC:

1599

AN:

251382

Hom.:

AF XY:

0.00647

AC XY:

879

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00370

Gnomad ASJ exome

AF:

0.00804

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00730

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.00700

GnomAD4 exome

AF:

0.00812

AC:

11874

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00780

AC XY:

5673

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.00903

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00670

Gnomad4 NFE exome

AF:

0.00956

Gnomad4 OTH exome

AF:

0.00747

GnomAD4 genome

AF:

0.00601

AC:

913

AN:

152038

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

431

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00157

Gnomad4 AMR

AF:

0.00563

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00595

Gnomad4 NFE

AF:

0.00943

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00809

Hom.:

Bravo

AF:

0.00535

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00849

AC:

ExAC

AF:

0.00696

AC:

845

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00943

EpiControl

AF:

0.00919

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.029

Eigen

Benign

-0.22

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.89

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.020

REVEL

Benign

0.062

Sift

Benign

0.52

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.13

MVP

0.068

MPC

0.43

ClinPred

0.027

GERP RS

5.3

Varity_R

0.16

gMVP

0.57

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