Variant rs8176785 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006157.5(NELL1):c.245G>A(p.Arg82Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 1,613,384 control chromosomes in the GnomAD database, including 449,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.63 ( 34060 hom., cov: 31)

Exomes 𝑓: 0.75 ( 415156 hom. )

Consequence

NELL1
NM_006157.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.46

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.0671424E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NELL1	NM_006157.5 linkuse as main transcript	c.245G>A	p.Arg82Gln	missense_variant	3/20	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1 linkuse as main transcript	c.329G>A	p.Arg110Gln	missense_variant	4/21		NP_001275642.1
NELL1	NM_201551.2 linkuse as main transcript	c.245G>A	p.Arg82Gln	missense_variant	3/19		NP_963845.1
NELL1	NM_001288714.1 linkuse as main transcript	c.245G>A	p.Arg82Gln	missense_variant	3/19		NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10 linkuse as main transcript	c.245G>A	p.Arg82Gln	missense_variant	3/20	1	NM_006157.5	ENSP00000349654	P1	Q92832-1

Frequencies

GnomAD3 genomes

AF:

0.635

AC:

96482

AN:

151870

Hom.:

34056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.819

Gnomad ASJ

AF:

0.845

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.751

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.755

Gnomad OTH

AF:

0.693

GnomAD3 exomes

AF:

0.747

AC:

187642

AN:

251220

Hom.:

72413

AF XY:

0.751

AC XY:

101977

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.881

Gnomad ASJ exome

AF:

0.827

Gnomad EAS exome

AF:

0.856

Gnomad SAS exome

AF:

0.754

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.760

Gnomad OTH exome

AF:

0.774

GnomAD4 exome

AF:

0.749

AC:

1094656

AN:

1461396

Hom.:

415156

Cov.:

AF XY:

0.751

AC XY:

545969

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.874

Gnomad4 ASJ exome

AF:

0.827

Gnomad4 EAS exome

AF:

0.859

Gnomad4 SAS exome

AF:

0.754

Gnomad4 FIN exome

AF:

0.662

Gnomad4 NFE exome

AF:

0.756

Gnomad4 OTH exome

AF:

0.746

GnomAD4 genome

AF:

0.635

AC:

96503

AN:

151988

Hom.:

34060

Cov.:

AF XY:

0.638

AC XY:

47408

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.819

Gnomad4 ASJ

AF:

0.845

Gnomad4 EAS

AF:

0.852

Gnomad4 SAS

AF:

0.751

Gnomad4 FIN

AF:

0.652

Gnomad4 NFE

AF:

0.755

Gnomad4 OTH

AF:

0.693

Alfa

AF:

0.742

Hom.:

78210

Bravo

AF:

0.634

TwinsUK

AF:

0.745

AC:

2764

ALSPAC

AF:

0.763

AC:

2939

ESP6500AA

AF:

0.302

AC:

1331

ESP6500EA

AF:

0.756

AC:

6504

ExAC

AF:

0.736

AC:

89362

Asia WGS

AF:

0.780

AC:

2714

AN:

3478

EpiCase

AF:

0.770

EpiControl

AF:

0.774

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

.;T;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T;T;T

MetaRNN

Benign

8.1e-7

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;.;L;L

MutationTaster

Benign

0.58

P;P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Benign

0.084

Sift

Benign

0.17

T;T;T;T

Sift4G

Uncertain

0.028

D;D;D;D

Polyphen

0.0070

B;.;B;B

Vest4

0.19

MPC

0.10

ClinPred

0.027

GERP RS

3.1

Varity_R

0.088

gMVP

0.47

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over