11-20677383-C-G

Position:

• chr11-20677383-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELL1	NM_006157.5	c.56-549C>G		intron_variant		ENST00000357134.10
NELL1	NM_001288713.1	c.140-549C>G		intron_variant
NELL1	NM_001288714.1	c.56-549C>G		intron_variant
NELL1	NM_201551.2	c.56-549C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELL1	ENST00000357134.10	c.56-549C>G		intron_variant		1	NM_006157.5	P1
NELL1	ENST00000532434.5	c.56-549C>G		intron_variant		1
NELL1	ENST00000298925.9	c.140-549C>G		intron_variant		2
NELL1	ENST00000325319.9	c.56-549C>G		intron_variant		2

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

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.700

Alfa AF: 0.720 Hom.: 19447

Bravo AF: 0.684

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.87
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs1793004; hg19: chr11-20698929;