rs12279250

Positions:

• chr11-21543533-T-C

Variant summary

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

The NM_006157.5(NELL1):​c.1786+9019T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,784 control chromosomes in the GnomAD database, including 12,300 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 0.38 (12300 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELL1	NM_006157.5	c.1786+9019T>C		intron_variant		ENST00000357134.10
NELL1	NM_001288713.1	c.1870+9019T>C		intron_variant
NELL1	NM_001288714.1	c.1615+9019T>C		intron_variant
NELL1	NM_201551.2	c.1646-16656T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELL1	ENST00000357134.10	c.1786+9019T>C		intron_variant		1	NM_006157.5	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57491 AN: 151664 Hom.: 12301 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.379 AC: 57515 AN: 151784 Hom.: 12300 Cov.: 32 AF XY: 0.377 AC XY: 27959 AN XY: 74152

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.385

Alfa AF: 0.432 Hom.: 3807

Bravo AF: 0.357

Asia WGS AF: 0.309 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.79

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: rs12279250; hg19: chr11-21565079;