rs1377741

Positions:

• chr11-21225670-A-T

Variant summary

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

The NM_006157.5(NELL1):​c.1427-3662A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,790 control chromosomes in the GnomAD database, including 17,566 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 0.48 (17566 hom., cov: 31)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1427-3662A>T		intron_variant		ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1511-3662A>T		intron_variant			NP_001275642.1
NELL1	NM_001288714.1	c.1256-3662A>T		intron_variant			NP_001275643.1
NELL1	NM_201551.2	c.1427-3662A>T		intron_variant			NP_963845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.1427-3662A>T		intron_variant		1	NM_006157.5	ENSP00000349654	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72346 AN: 151670 Hom.: 17544 Cov.: 31

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.477 AC: 72403 AN: 151790 Hom.: 17566 Cov.: 31 AF XY: 0.479 AC XY: 35541 AN XY: 74148

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.481

Alfa AF: 0.498 Hom.: 2370

Bravo AF: 0.462

Asia WGS AF: 0.416 AC: 1444 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.63

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: rs1377741; hg19: chr11-21247216; COSMIC: COSV54318134;