11-21365718-T-C

Variant names:

• chr11-21365718-T-C
• rs1945404
• NM_006157.5:c.1550-5135T>C

Variant summary

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

The NM_006157.5(NELL1):​c.1550-5135T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,760 control chromosomes in the GnomAD database, including 30,103 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 0.63 (30103 hom., cov: 30)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.70
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1550-5135T>C		intron_variant	Intron 14 of 19	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1634-5135T>C		intron_variant	Intron 15 of 20		NP_001275642.1
NELL1	NM_201551.2	c.1550-5135T>C		intron_variant	Intron 14 of 18		NP_963845.1
NELL1	NM_001288714.1	c.1379-5135T>C		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.1550-5135T>C		intron_variant	Intron 14 of 19	1	NM_006157.5	ENSP00000349654.5

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95287 AN: 151642 Hom.: 30089 Cov.: 30

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.628 AC: 95330 AN: 151760 Hom.: 30103 Cov.: 30 AF XY: 0.628 AC XY: 46537 AN XY: 74130

African (AFR) AF: 0.666 AC: 27551 AN: 41372

American (AMR) AF: 0.506 AC: 7703 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2360 AN: 3468

East Asian (EAS) AF: 0.609 AC: 3134 AN: 5142

South Asian (SAS) AF: 0.609 AC: 2921 AN: 4794

European-Finnish (FIN) AF: 0.669 AC: 7035 AN: 10516

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42570 AN: 67932

Other (OTH) AF: 0.626 AC: 1316 AN: 2102

Alfa AF: 0.613 Hom.: 21182

Bravo AF: 0.617

Asia WGS AF: 0.621 AC: 2157 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.6
DANN	Benign	0.68
PhyloP100		2.7
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: rs1945404; hg19: chr11-21387264;