chr11-21404866-G-A

Position:

• chr11-21404866-G-A

Variant summary

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

The NM_006157.5(NELL1):​c.1645+33918G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,840 control chromosomes in the GnomAD database, including 13,456 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 0.41 (13456 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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]

NELL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1645+33918G>A		intron_variant		ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1729+33918G>A		intron_variant			NP_001275642.1
NELL1	NM_201551.2	c.1645+33918G>A		intron_variant			NP_963845.1
NELL1	NM_001288714.1	c.1474+33918G>A		intron_variant			NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.1645+33918G>A		intron_variant		1	NM_006157.5	ENSP00000349654.5

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62323 AN: 151722 Hom.: 13442 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.411 AC: 62379 AN: 151840 Hom.: 13456 Cov.: 32 AF XY: 0.404 AC XY: 29972 AN XY: 74184

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.0798

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.419

Alfa AF: 0.388 Hom.: 15097

Bravo AF: 0.414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.38

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: rs1981410; hg19: chr11-21426412;