11-20903493-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006157.5(NELL1):c.604-14689T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,870 control chromosomes in the GnomAD database, including 29,788 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 (29788 hom., cov: 31)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

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]

LOC105376585 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELL1	NM_006157.5	c.604-14689T>G		intron_variant		ENST00000357134.10
LOC105376585	XR_931106.3	n.85-122A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELL1	ENST00000357134.10	c.604-14689T>G		intron_variant		1	NM_006157.5	P1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86293 AN: 151752 Hom.: 29780 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.568 AC: 86312 AN: 151870 Hom.: 29788 Cov.: 31 AF XY: 0.570 AC XY: 42257 AN XY: 74188

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.609

Alfa AF: 0.741 Hom.: 82435

Bravo AF: 0.540

Asia WGS AF: 0.568 AC: 1975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.4
Dann	Benign	0.72

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: rs10766743; hg19: chr11-20925039;