rs4569005

Variant names:

• chr11-21037185-C-T
• rs4569005
• NM_006157.5:c.1301-76404C>T

Variant summary

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

The NM_006157.5(NELL1):​c.1301-76404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,934 control chromosomes in the GnomAD database, including 3,361 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3361 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.535
• Publications: 4 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 (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 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.1301-76404C>T		intron	N/A	NP_006148.2
	NELL1	NM_001288713.1		c.1385-76404C>T		intron	N/A	NP_001275642.1
	NELL1	NM_201551.2		c.1301-76404C>T		intron	N/A	NP_963845.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	ENST00000357134.10	TSL:1 MANE Select	c.1301-76404C>T		intron	N/A	ENSP00000349654.5
	NELL1	ENST00000532434.5	TSL:1	c.1301-76404C>T		intron	N/A	ENSP00000437170.1
	NELL1	ENST00000298925.9	TSL:2	c.1385-76404C>T		intron	N/A	ENSP00000298925.5

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29524 AN: 151816 Hom.: 3354 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0427

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.195 AC: 29555 AN: 151934 Hom.: 3361 Cov.: 32 AF XY: 0.196 AC XY: 14531 AN XY: 74244

African (AFR) AF: 0.318 AC: 13165 AN: 41442

American (AMR) AF: 0.140 AC: 2129 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 447 AN: 3470

East Asian (EAS) AF: 0.0426 AC: 221 AN: 5184

South Asian (SAS) AF: 0.189 AC: 909 AN: 4814

European-Finnish (FIN) AF: 0.187 AC: 1970 AN: 10558

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10222 AN: 67904

Other (OTH) AF: 0.161 AC: 338 AN: 2102

Alfa AF: 0.162 Hom.: 6132

Bravo AF: 0.193

Asia WGS AF: 0.139 AC: 483 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.6
DANN	Benign	0.49
PhyloP100		0.54
Mutation Taster		=100/0	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: rs4569005; hg19: chr11-21058731;