rs11026037

Variant names:

• chr11-21345684-C-T
• rs11026037
• NM_006157.5:c.1550-25169C>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.1550-25169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,228 control chromosomes in the GnomAD database, including 1,837 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 0.14 (1837 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1550-25169C>T		intron_variant	Intron 14 of 19	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1634-25169C>T		intron_variant	Intron 15 of 20		NP_001275642.1
NELL1	NM_201551.2	c.1550-25169C>T		intron_variant	Intron 14 of 18		NP_963845.1
NELL1	NM_001288714.1	c.1379-25169C>T		intron_variant	Intron 13 of 18		NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.1550-25169C>T		intron_variant	Intron 14 of 19	1	NM_006157.5	ENSP00000349654.5

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21439 AN: 152110 Hom.: 1838 Cov.: 32

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0453

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.141 AC: 21432 AN: 152228 Hom.: 1837 Cov.: 32 AF XY: 0.141 AC XY: 10461 AN XY: 74426

African (AFR) AF: 0.0439 AC: 1822 AN: 41548

American (AMR) AF: 0.137 AC: 2088 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 681 AN: 3468

East Asian (EAS) AF: 0.0455 AC: 235 AN: 5170

South Asian (SAS) AF: 0.140 AC: 678 AN: 4826

European-Finnish (FIN) AF: 0.160 AC: 1691 AN: 10598

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.200 AC: 13581 AN: 68016

Other (OTH) AF: 0.154 AC: 326 AN: 2114

Alfa AF: 0.165 Hom.: 600

Bravo AF: 0.134

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.76
DANN	Benign	0.76
PhyloP100		-0.15
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: rs11026037; hg19: chr11-21367230; COSMIC: COSV54260085;