rs4922847

Positions:

• chr11-21570682-C-A
• chr11-21570682-C-G

Variant summary

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

The NM_006157.5(NELL1):​c.1981-82C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 1,414,380 control chromosomes in the GnomAD database, including 443,168 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 0.67 (37386 hom., cov: 31)
  • Exomes 𝑓: 0.80 (405782 hom.)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELL1	NM_006157.5	c.1981-82C>A		intron_variant		ENST00000357134.10
NELL1	NM_001288713.1	c.2065-82C>A		intron_variant
NELL1	NM_001288714.1	c.1810-82C>A		intron_variant
NELL1	NM_201551.2	c.1840-82C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELL1	ENST00000357134.10	c.1981-82C>A		intron_variant		1	NM_006157.5	P1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 101965 AN: 151512 Hom.: 37383 Cov.: 31

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.698

GnomAD4 exome AF: 0.796 AC: 1004749 AN: 1262750 Hom.: 405782 AF XY: 0.793 AC XY: 496158 AN XY: 626018

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.851

Gnomad4 EAS exome AF: 0.726

Gnomad4 SAS exome AF: 0.616

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.832

Gnomad4 OTH exome AF: 0.761

GnomAD4 genome AF: 0.673 AC: 101997 AN: 151630 Hom.: 37386 Cov.: 31 AF XY: 0.670 AC XY: 49633 AN XY: 74044

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.846

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.696

Alfa AF: 0.779 Hom.: 18670

Bravo AF: 0.650

Asia WGS AF: 0.588 AC: 2044 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.20

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: rs4922847; hg19: chr11-21592228; COSMIC: COSV54266639;