11-21345684-C-T

Position:

• chr11-21345684-C-T

Variant summary

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

The NM_006157.5(NELL1):​c.1550-25169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,228 control chromosomes in the GnomAD database, including 1,837 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 0.14 (1837 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELL1	NM_006157.5	c.1550-25169C>T		intron_variant		ENST00000357134.10
NELL1	NM_001288713.1	c.1634-25169C>T		intron_variant
NELL1	NM_001288714.1	c.1379-25169C>T		intron_variant
NELL1	NM_201551.2	c.1550-25169C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELL1	ENST00000357134.10	c.1550-25169C>T		intron_variant		1	NM_006157.5	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21439 AN: 152110 Hom.: 1838 Cov.: 32

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0453

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.141 AC: 21432 AN: 152228 Hom.: 1837 Cov.: 32 AF XY: 0.141 AC XY: 10461 AN XY: 74426

Gnomad4 AFR AF: 0.0439

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0455

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.154

Alfa AF: 0.168 Hom.: 600

Bravo AF: 0.134

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.76
DANN	Benign	0.76

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: rs11026037; hg19: chr11-21367230; COSMIC: COSV54260085;