11-21543533-T-C

Variant names:

• chr11-21543533-T-C
• rs12279250
• NM_006157.5:c.1786+9019T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.85).
• 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 rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1786+9019T>C		intron_variant	Intron 16 of 19	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1870+9019T>C		intron_variant	Intron 17 of 20		NP_001275642.1
NELL1	NM_201551.2	c.1646-16656T>C		intron_variant	Intron 15 of 18		NP_963845.1
NELL1	NM_001288714.1	c.1615+9019T>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.1786+9019T>C		intron_variant	Intron 16 of 19	1	NM_006157.5	ENSP00000349654.5

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

African (AFR) AF: 0.197 AC: 8181 AN: 41458

American (AMR) AF: 0.337 AC: 5123 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1394 AN: 3468

East Asian (EAS) AF: 0.276 AC: 1407 AN: 5090

South Asian (SAS) AF: 0.360 AC: 1731 AN: 4806

European-Finnish (FIN) AF: 0.488 AC: 5152 AN: 10568

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33208 AN: 67868

Other (OTH) AF: 0.385 AC: 810 AN: 2106

Alfa AF: 0.434 Hom.: 26551

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
PhyloP100		1.8
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: rs12279250; hg19: chr11-21565079;