rs12577018

Variant names:

• chr11-21042776-C-T
• rs12577018
• NM_006157.5:c.1301-70813C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006157.5(NELL1):​c.1301-70813C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,104 control chromosomes in the GnomAD database, including 2,061 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 0.15 (2061 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1301-70813C>T		intron_variant	Intron 12 of 19	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1385-70813C>T		intron_variant	Intron 13 of 20		NP_001275642.1
NELL1	NM_201551.2	c.1301-70813C>T		intron_variant	Intron 12 of 18		NP_963845.1
NELL1	NM_001288714.1	c.1130-70813C>T		intron_variant	Intron 11 of 18		NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.1301-70813C>T		intron_variant	Intron 12 of 19	1	NM_006157.5	ENSP00000349654.5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22432 AN: 151986 Hom.: 2051 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.148 AC: 22463 AN: 152104 Hom.: 2061 Cov.: 32 AF XY: 0.146 AC XY: 10860 AN XY: 74348

African (AFR) AF: 0.239 AC: 9913 AN: 41488

American (AMR) AF: 0.103 AC: 1566 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3470

East Asian (EAS) AF: 0.118 AC: 607 AN: 5164

South Asian (SAS) AF: 0.147 AC: 707 AN: 4810

European-Finnish (FIN) AF: 0.116 AC: 1228 AN: 10592

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7480 AN: 67996

Other (OTH) AF: 0.126 AC: 265 AN: 2110

Alfa AF: 0.121 Hom.: 2303

Bravo AF: 0.150

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.69
PhyloP100		0.22
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: rs12577018; hg19: chr11-21064322;