rs4319515

Variant names:

• chr11-21556821-T-C
• rs4319515
• NM_006157.5:c.1787-3368T>C

Variant summary

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

The NM_006157.5(NELL1):​c.1787-3368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,754 control chromosomes in the GnomAD database, including 11,929 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 0.37 (11929 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1787-3368T>C		intron_variant	Intron 16 of 19	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1871-3368T>C		intron_variant	Intron 17 of 20		NP_001275642.1
NELL1	NM_201551.2	c.1646-3368T>C		intron_variant	Intron 15 of 18		NP_963845.1
NELL1	NM_001288714.1	c.1616-3368T>C		intron_variant	Intron 15 of 18		NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.1787-3368T>C		intron_variant	Intron 16 of 19	1	NM_006157.5	ENSP00000349654.5

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56170 AN: 151634 Hom.: 11933 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.370 AC: 56176 AN: 151754 Hom.: 11929 Cov.: 32 AF XY: 0.368 AC XY: 27327 AN XY: 74172

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.370

Alfa AF: 0.456 Hom.: 32940

Bravo AF: 0.347

Asia WGS AF: 0.302 AC: 1052 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.56

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: rs4319515; hg19: chr11-21578367;