11-20679229-C-G

Variant names:

• chr11-20679229-C-G
• rs951199
• NM_006157.5:c.184+1169C>G

Variant summary

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

The NM_006157.5(NELL1):​c.184+1169C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,998 control chromosomes in the GnomAD database, including 32,401 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 0.64 (32401 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.184+1169C>G		intron_variant	Intron 2 of 19	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.268+1169C>G		intron_variant	Intron 3 of 20		NP_001275642.1
NELL1	NM_201551.2	c.184+1169C>G		intron_variant	Intron 2 of 18		NP_963845.1
NELL1	NM_001288714.1	c.184+1169C>G		intron_variant	Intron 2 of 18		NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.184+1169C>G		intron_variant	Intron 2 of 19	1	NM_006157.5	ENSP00000349654.5
NELL1	ENST00000532434.5	c.184+1169C>G		intron_variant	Intron 2 of 18	1		ENSP00000437170.1
NELL1	ENST00000298925.9	c.268+1169C>G		intron_variant	Intron 3 of 20	2		ENSP00000298925.5
NELL1	ENST00000325319.9	c.184+1169C>G		intron_variant	Intron 2 of 18	2		ENSP00000317837.5

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97333 AN: 151880 Hom.: 32388 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.641 AC: 97367 AN: 151998 Hom.: 32401 Cov.: 32 AF XY: 0.639 AC XY: 47428 AN XY: 74278

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.661

Alfa AF: 0.672 Hom.: 4376

Bravo AF: 0.630

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.015
DANN	Benign	0.40

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: rs951199; hg19: chr11-20700775;