rs1987307

Positions:

• chr11-20952310-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006157.5(NELL1):​c.1171+4875A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 152,248 control chromosomes in the GnomAD database, including 417 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 0.064 (417 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1171+4875A>C		intron_variant		ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1255+4875A>C		intron_variant			NP_001275642.1
NELL1	NM_001288714.1	c.1000+4875A>C		intron_variant			NP_001275643.1
NELL1	NM_201551.2	c.1171+4875A>C		intron_variant			NP_963845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.1171+4875A>C		intron_variant		1	NM_006157.5	ENSP00000349654	P1

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9726 AN: 152130 Hom.: 417 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.0424

Gnomad FIN AF: 0.0842

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0921

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0639 AC: 9722 AN: 152248 Hom.: 417 Cov.: 32 AF XY: 0.0631 AC XY: 4694 AN XY: 74428

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.0449

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.0847

Gnomad4 SAS AF: 0.0423

Gnomad4 FIN AF: 0.0842

Gnomad4 NFE AF: 0.0921

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0827 Hom.: 312

Bravo AF: 0.0597

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.57

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: rs1987307; hg19: chr11-20973856;