11-21421613-C-T

Variant names:

• chr11-21421613-C-T
• rs1945427
• NM_006157.5:c.1645+50665C>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.1645+50665C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,724 control chromosomes in the GnomAD database, including 21,180 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 0.50 (21180 hom., cov: 30)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1645+50665C>T		intron_variant	Intron 15 of 19	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1729+50665C>T		intron_variant	Intron 16 of 20		NP_001275642.1
NELL1	NM_201551.2	c.1645+50665C>T		intron_variant	Intron 15 of 18		NP_963845.1
NELL1	NM_001288714.1	c.1474+50665C>T		intron_variant	Intron 14 of 18		NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.1645+50665C>T		intron_variant	Intron 15 of 19	1	NM_006157.5	ENSP00000349654.5

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76111 AN: 151604 Hom.: 21152 Cov.: 30

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.502 AC: 76184 AN: 151724 Hom.: 21180 Cov.: 30 AF XY: 0.499 AC XY: 37006 AN XY: 74096

African (AFR) AF: 0.756 AC: 31283 AN: 41364

American (AMR) AF: 0.444 AC: 6764 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1642 AN: 3462

East Asian (EAS) AF: 0.458 AC: 2336 AN: 5104

South Asian (SAS) AF: 0.507 AC: 2435 AN: 4804

European-Finnish (FIN) AF: 0.344 AC: 3605 AN: 10492

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26607 AN: 67944

Other (OTH) AF: 0.506 AC: 1067 AN: 2110

Alfa AF: 0.436 Hom.: 30400

Bravo AF: 0.518

Asia WGS AF: 0.492 AC: 1712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		-0.75
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: rs1945427; hg19: chr11-21443159;