Variant 11-20918209-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006157.5(NELL1):c.631T>G(p.Phe211Val) variant causes a missense change. The variant allele was found at a frequency of 0.00366 in 1,601,332 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.020 ( 119 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 87 hom. )

Consequence

NELL1
NM_006157.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.75

Variant links:

Genes affected

NELL1 (HGNC:7750): (neural EGFL like 1) This gene encodes a cytoplasmic protein that contains epidermal growth factor (EGF)-like repeats. The encoded heterotrimeric protein may be involved in cell growth regulation and differentiation. A similar protein in rodents is involved in craniosynostosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

NELL1 links:

LOC105376585 (HGNC:):

LOC105376585 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004867673).

BP6

Variant 11-20918209-T-G is Benign according to our data. Variant chr11-20918209-T-G is described in ClinVar as [Benign]. Clinvar id is 768437.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELL1	NM_006157.5 linkuse as main transcript	c.631T>G	p.Phe211Val	missense_variant	6/20	ENST00000357134.10
LOC105376585	XR_931106.3 linkuse as main transcript	n.84+8504A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELL1	ENST00000357134.10 linkuse as main transcript	c.631T>G	p.Phe211Val	missense_variant	6/20	1	NM_006157.5	P1	Q92832-1

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3106

AN:

151928

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0711

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00749

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00495

AC:

1238

AN:

249910

Hom.:

AF XY:

0.00358

AC XY:

483

AN XY:

135082

show subpopulations

Gnomad AFR exome

AF:

0.0666

Gnomad AMR exome

AF:

0.00395

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000295

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000886

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00190

AC:

2751

AN:

1449286

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

1157

AN XY:

721828

show subpopulations

Gnomad4 AFR exome

AF:

0.0664

Gnomad4 AMR exome

AF:

0.00428

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000326

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000527

Gnomad4 OTH exome

AF:

0.00457

GnomAD4 genome

AF:

0.0205

AC:

3110

AN:

152046

Hom.:

119

Cov.:

AF XY:

0.0191

AC XY:

1422

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0710

Gnomad4 AMR

AF:

0.00748

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.00357

Hom.:

Bravo

AF:

0.0237

ESP6500AA

AF:

0.0679

AC:

299

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00627

AC:

761

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000178

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

0.20

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.020

Cadd

Benign

Dann

Benign

0.97

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D;D

MetaRNN

Benign

0.0049

T;T;T;T

MetaSVM

Benign

-0.70

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.74

N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.42

T;T;T;T

Sift4G

Benign

0.87

T;T;T;T

Polyphen

1.0

D;.;D;B

Vest4

0.85

MVP

0.85

MPC

0.12

ClinPred

0.036

GERP RS

5.9

Varity_R

0.29

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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