11-20677383-C-G

Variant names:

• chr11-20677383-C-G
• rs1793004
• NM_006157.5:c.56-549C>G

Variant summary

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

The NM_006157.5(NELL1):​c.56-549C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,020 control chromosomes in the GnomAD database, including 36,380 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 0.69 (36380 hom., cov: 31)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 16 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.74 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.56-549C>G		intron	N/A	NP_006148.2
	NELL1	NM_001288713.1		c.140-549C>G		intron	N/A	NP_001275642.1
	NELL1	NM_201551.2		c.56-549C>G		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.56-549C>G		intron	N/A	ENSP00000349654.5
	NELL1	ENST00000532434.5	TSL:1	c.56-549C>G		intron	N/A	ENSP00000437170.1
	NELL1	ENST00000298925.9	TSL:2	c.140-549C>G		intron	N/A	ENSP00000298925.5

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104583 AN: 151902 Hom.: 36370 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.688 AC: 104625 AN: 152020 Hom.: 36380 Cov.: 31 AF XY: 0.685 AC XY: 50891 AN XY: 74318

African (AFR) AF: 0.625 AC: 25902 AN: 41436

American (AMR) AF: 0.668 AC: 10201 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2558 AN: 3472

East Asian (EAS) AF: 0.487 AC: 2512 AN: 5154

South Asian (SAS) AF: 0.626 AC: 3010 AN: 4812

European-Finnish (FIN) AF: 0.687 AC: 7272 AN: 10586

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50649 AN: 67978

Other (OTH) AF: 0.700 AC: 1470 AN: 2100

Alfa AF: 0.720 Hom.: 19447

Bravo AF: 0.684

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.87
DANN	Benign	0.64
PhyloP100		-0.47
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: rs1793004; hg19: chr11-20698929;