11-20876844-A-G

Variant names:

• chr11-20876844-A-G
• rs10766739
• NM_006157.5:c.507-8600A>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.507-8600A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,104 control chromosomes in the GnomAD database, including 28,546 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 0.57 (28546 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 6 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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.736 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.507-8600A>G		intron	N/A	NP_006148.2
	NELL1	NM_001288713.1		c.591-8600A>G		intron	N/A	NP_001275642.1
	NELL1	NM_201551.2		c.507-8600A>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.507-8600A>G		intron	N/A	ENSP00000349654.5
	NELL1	ENST00000532434.5	TSL:1	c.507-8600A>G		intron	N/A	ENSP00000437170.1
	NELL1	ENST00000298925.9	TSL:2	c.591-8600A>G		intron	N/A	ENSP00000298925.5

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86905 AN: 151986 Hom.: 28544 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.571 AC: 86917 AN: 152104 Hom.: 28546 Cov.: 32 AF XY: 0.572 AC XY: 42544 AN XY: 74336

African (AFR) AF: 0.222 AC: 9223 AN: 41504

American (AMR) AF: 0.601 AC: 9186 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2415 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3072 AN: 5168

South Asian (SAS) AF: 0.695 AC: 3348 AN: 4818

European-Finnish (FIN) AF: 0.680 AC: 7186 AN: 10572

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50398 AN: 67964

Other (OTH) AF: 0.613 AC: 1295 AN: 2114

Alfa AF: 0.658 Hom.: 68070

Bravo AF: 0.547

Asia WGS AF: 0.630 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.2
DANN	Benign	0.81
PhyloP100		0.0030
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: rs10766739; hg19: chr11-20898390;