11-21023350-C-T

Variant names:

• chr11-21023350-C-T
• rs7122403
• NM_006157.5:c.1300+62790C>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.1300+62790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 151,866 control chromosomes in the GnomAD database, including 5,146 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 0.15 (5146 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	NM_006157.5	MANE Select	c.1300+62790C>T		intron	N/A	NP_006148.2	Q92832-1
	NELL1	NM_001288713.1		c.1384+62790C>T		intron	N/A	NP_001275642.1	Q92832
	NELL1	NM_201551.2		c.1300+62790C>T		intron	N/A	NP_963845.1	Q92832-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	ENST00000357134.10	TSL:1 MANE Select	c.1300+62790C>T		intron	N/A	ENSP00000349654.5	Q92832-1
	NELL1	ENST00000532434.5	TSL:1	c.1300+62790C>T		intron	N/A	ENSP00000437170.1	Q92832-2
	NELL1	ENST00000298925.9	TSL:2	c.1384+62790C>T		intron	N/A	ENSP00000298925.5	J3KNC5

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22138 AN: 151748 Hom.: 5129 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.0413

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0000947

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.00493

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.146 AC: 22199 AN: 151866 Hom.: 5146 Cov.: 32 AF XY: 0.141 AC XY: 10495 AN XY: 74198

African (AFR) AF: 0.494 AC: 20455 AN: 41398

American (AMR) AF: 0.0618 AC: 940 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0413 AC: 143 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.0123 AC: 59 AN: 4814

European-Finnish (FIN) AF: 0.0000947 AC: 1 AN: 10564

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.00493 AC: 335 AN: 67944

Other (OTH) AF: 0.115 AC: 243 AN: 2108

Alfa AF: 0.0469 Hom.: 1599

Bravo AF: 0.166

Asia WGS AF: 0.0410 AC: 142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.5
DANN	Benign	0.51
PhyloP100		-0.31
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: rs7122403; hg19: chr11-21044896;