11-20849190-C-T

Variant names:

• chr11-20849190-C-T
• rs7927476
• NM_006157.5:c.506+1437C>T

Variant summary

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

The NM_006157.5(NELL1):​c.506+1437C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,094 control chromosomes in the GnomAD database, including 45,083 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 0.75 (45083 hom., cov: 33)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.506+1437C>T		intron_variant	Intron 4 of 19	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.590+1437C>T		intron_variant	Intron 5 of 20		NP_001275642.1
NELL1	NM_201551.2	c.506+1437C>T		intron_variant	Intron 4 of 18		NP_963845.1
NELL1	NM_001288714.1	c.336-36254C>T		intron_variant	Intron 3 of 18		NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.506+1437C>T		intron_variant	Intron 4 of 19	1	NM_006157.5	ENSP00000349654.5

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114635 AN: 151976 Hom.: 45072 Cov.: 33

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.754 AC: 114678 AN: 152094 Hom.: 45083 Cov.: 33 AF XY: 0.748 AC XY: 55625 AN XY: 74372

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.797

Alfa AF: 0.856 Hom.: 57295

Bravo AF: 0.734

Asia WGS AF: 0.753 AC: 2623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.77

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: rs7927476; hg19: chr11-20870736;