11-20783740-G-A

Variant names:

• chr11-20783740-G-A
• rs8176785
• NM_006157.5:c.245G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R82G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.63 (34060 hom., cov: 31)
  • Exomes 𝑓: 0.75 (415156 hom.)
• Consequence: NELL1 NM_006157.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• Publications: 35 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006157.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	NM_006157.5	MANE Select	c.245G>A	p.Arg82Gln	missense	Exon 3 of 20	NP_006148.2
	NELL1	NM_001288713.1		c.329G>A	p.Arg110Gln	missense	Exon 4 of 21	NP_001275642.1
	NELL1	NM_201551.2		c.245G>A	p.Arg82Gln	missense	Exon 3 of 19	NP_963845.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	ENST00000357134.10	TSL:1 MANE Select	c.245G>A	p.Arg82Gln	missense	Exon 3 of 20	ENSP00000349654.5
	NELL1	ENST00000532434.5	TSL:1	c.245G>A	p.Arg82Gln	missense	Exon 3 of 19	ENSP00000437170.1
	NELL1	ENST00000298925.9	TSL:2	c.329G>A	p.Arg110Gln	missense	Exon 4 of 21	ENSP00000298925.5

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96482 AN: 151870 Hom.: 34056 Cov.: 31

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

GnomAD2 exomes AF: 0.747 AC: 187642 AN: 251220 AF XY: 0.751

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 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.: 41 AF XY: 0.751 AC XY: 545969 AN XY: 727024

African (AFR) AF: 0.284 AC: 9516 AN: 33470

American (AMR) AF: 0.874 AC: 39075 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 21609 AN: 26130

East Asian (EAS) AF: 0.859 AC: 34112 AN: 39692

South Asian (SAS) AF: 0.754 AC: 64996 AN: 86226

European-Finnish (FIN) AF: 0.662 AC: 35333 AN: 53392

Middle Eastern (MID) AF: 0.798 AC: 4605 AN: 5768

European-Non Finnish (NFE) AF: 0.756 AC: 840352 AN: 1111618

Other (OTH) AF: 0.746 AC: 45058 AN: 60384

GnomAD4 genome AF: 0.635 AC: 96503 AN: 151988 Hom.: 34060 Cov.: 31 AF XY: 0.638 AC XY: 47408 AN XY: 74316

African (AFR) AF: 0.301 AC: 12473 AN: 41432

American (AMR) AF: 0.819 AC: 12517 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2929 AN: 3468

East Asian (EAS) AF: 0.852 AC: 4394 AN: 5160

South Asian (SAS) AF: 0.751 AC: 3621 AN: 4824

European-Finnish (FIN) AF: 0.652 AC: 6877 AN: 10548

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51314 AN: 67966

Other (OTH) AF: 0.693 AC: 1459 AN: 2104

Alfa AF: 0.737 Hom.: 101495

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	8.1e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.084
Sift	Benign	0.17	T
Sift4G	Uncertain	0.028	D
Polyphen		0.0070	B
Vest4		0.19
MPC		0.10
ClinPred		0.027	T
GERP RS		3.1
Varity_R		0.088
gMVP		0.47
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8176785; hg19: chr11-20805286; COSMIC: COSV107331938;