NM_006157.5:c.998-2067C>T

Variant names:

• chr11-20935719-C-T
• rs7122630
• NM_006157.5:c.998-2067C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006157.5(NELL1):​c.998-2067C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 152,074 control chromosomes in the GnomAD database, including 44,259 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 (44197 hom., cov: 31)
  • Exomes 𝑓: 0.84 (62 hom.)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006157.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	NM_006157.5	MANE Select	c.998-2067C>T		intron	N/A	NP_006148.2
	NELL1	NM_001288713.1		c.1082-2067C>T		intron	N/A	NP_001275642.1
	NELL1	NM_201551.2		c.998-2067C>T		intron	N/A	NP_963845.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	ENST00000357134.10	TSL:1 MANE Select	c.998-2067C>T		intron	N/A	ENSP00000349654.5
	NELL1	ENST00000532434.5	TSL:1	c.998-2067C>T		intron	N/A	ENSP00000437170.1
	NELL1	ENST00000530672.1	TSL:4	n.24C>T		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113274 AN: 151784 Hom.: 44170 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.743

GnomAD4 exome AF: 0.837 AC: 144 AN: 172 Hom.: 62 Cov.: 0 AF XY: 0.770 AC XY: 77 AN XY: 100

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.750 AC: 3 AN: 4

European-Finnish (FIN) AF: 0.935 AC: 58 AN: 62

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.761 AC: 70 AN: 92

Other (OTH) AF: 1.00 AC: 8 AN: 8

GnomAD4 genome AF: 0.746 AC: 113338 AN: 151902 Hom.: 44197 Cov.: 31 AF XY: 0.749 AC XY: 55625 AN XY: 74240

African (AFR) AF: 0.508 AC: 21013 AN: 41358

American (AMR) AF: 0.839 AC: 12806 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2414 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5145 AN: 5162

South Asian (SAS) AF: 0.827 AC: 3973 AN: 4806

European-Finnish (FIN) AF: 0.848 AC: 8969 AN: 10580

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56531 AN: 67952

Other (OTH) AF: 0.746 AC: 1572 AN: 2108

Alfa AF: 0.794 Hom.: 27949

Bravo AF: 0.737

Asia WGS AF: 0.896 AC: 3115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.61
PhyloP100		0.0030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7122630; hg19: chr11-20957265;