11-20903493-T-G

Variant names:

• chr11-20903493-T-G
• rs10766743
• NM_006157.5:c.604-14689T>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.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
• Publications: 4 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]

LOC105376585 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.604-14689T>G		intron	N/A	NP_006148.2
	NELL1	NM_001288713.1		c.688-14689T>G		intron	N/A	NP_001275642.1
	NELL1	NM_201551.2		c.604-14689T>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.604-14689T>G		intron	N/A	ENSP00000349654.5
	NELL1	ENST00000532434.5	TSL:1	c.604-14689T>G		intron	N/A	ENSP00000437170.1
	NELL1	ENST00000298925.9	TSL:2	c.688-14689T>G		intron	N/A	ENSP00000298925.5

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

African (AFR) AF: 0.158 AC: 6552 AN: 41454

American (AMR) AF: 0.623 AC: 9489 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2451 AN: 3468

East Asian (EAS) AF: 0.520 AC: 2677 AN: 5144

South Asian (SAS) AF: 0.645 AC: 3106 AN: 4816

European-Finnish (FIN) AF: 0.713 AC: 7514 AN: 10538

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52430 AN: 67906

Other (OTH) AF: 0.609 AC: 1283 AN: 2106

Alfa AF: 0.711 Hom.: 166020

Bravo AF: 0.540

Asia WGS AF: 0.568 AC: 1975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.72
PhyloP100		-0.23
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: rs10766743; hg19: chr11-20925039;