rs10833498

chr11-21299759-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.1549+70305T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,976 control chromosomes in the GnomAD database, including 5,257 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 0.24 (5257 hom., cov: 31)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELL1	NM_006157.5	c.1549+70305T>C		intron_variant		ENST00000357134.10
NELL1	NM_001288713.1	c.1633+70305T>C		intron_variant
NELL1	NM_001288714.1	c.1378+70305T>C		intron_variant
NELL1	NM_201551.2	c.1549+70305T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELL1	ENST00000357134.10	c.1549+70305T>C		intron_variant		1	NM_006157.5	P1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36057 AN: 151858 Hom.: 5254 Cov.: 31

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.237 AC: 36072 AN: 151976 Hom.: 5257 Cov.: 31 AF XY: 0.236 AC XY: 17561 AN XY: 74288

Gnomad4 AFR AF: 0.0716

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.268

Alfa AF: 0.304 Hom.: 15090

Bravo AF: 0.235

Asia WGS AF: 0.217 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.71
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: rs10833498; hg19: chr11-21321305;