11-21548178-T-C

Position:

• chr11-21548178-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.1787-12011T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 151,708 control chromosomes in the GnomAD database, including 37,549 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 0.68 (37549 hom., cov: 31)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788

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 = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1787-12011T>C		intron_variant		ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1871-12011T>C		intron_variant			NP_001275642.1
NELL1	NM_001288714.1	c.1616-12011T>C		intron_variant			NP_001275643.1
NELL1	NM_201551.2	c.1646-12011T>C		intron_variant			NP_963845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.1787-12011T>C		intron_variant		1	NM_006157.5	ENSP00000349654	P1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102692 AN: 151590 Hom.: 37548 Cov.: 31

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.677 AC: 102715 AN: 151708 Hom.: 37549 Cov.: 31 AF XY: 0.676 AC XY: 50118 AN XY: 74138

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.698

Alfa AF: 0.730 Hom.: 7159

Bravo AF: 0.654

Asia WGS AF: 0.566 AC: 1970 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	7.6
DANN	Benign	0.83

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: rs7106789; hg19: chr11-21569724;