11-21041428-C-G

Variant names:

• chr11-21041428-C-G
• rs11025887
• NM_006157.5:c.1301-72161C>G

Variant summary

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

The NM_006157.5(NELL1):​c.1301-72161C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,946 control chromosomes in the GnomAD database, including 18,575 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 0.49 (18575 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 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.1301-72161C>G		intron	N/A	NP_006148.2	Q92832-1
	NELL1	NM_001288713.1		c.1385-72161C>G		intron	N/A	NP_001275642.1	Q92832
	NELL1	NM_201551.2		c.1301-72161C>G		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.1301-72161C>G		intron	N/A	ENSP00000349654.5	Q92832-1
	NELL1	ENST00000532434.5	TSL:1	c.1301-72161C>G		intron	N/A	ENSP00000437170.1	Q92832-2
	NELL1	ENST00000298925.9	TSL:2	c.1385-72161C>G		intron	N/A	ENSP00000298925.5	J3KNC5

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74346 AN: 151828 Hom.: 18571 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.489 AC: 74376 AN: 151946 Hom.: 18575 Cov.: 32 AF XY: 0.495 AC XY: 36757 AN XY: 74234

African (AFR) AF: 0.567 AC: 23497 AN: 41422

American (AMR) AF: 0.448 AC: 6832 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1393 AN: 3468

East Asian (EAS) AF: 0.715 AC: 3696 AN: 5166

South Asian (SAS) AF: 0.499 AC: 2405 AN: 4822

European-Finnish (FIN) AF: 0.491 AC: 5186 AN: 10570

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.439 AC: 29833 AN: 67940

Other (OTH) AF: 0.457 AC: 965 AN: 2112

Alfa AF: 0.472 Hom.: 2139

Bravo AF: 0.490

Asia WGS AF: 0.583 AC: 2023 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.55
PhyloP100		0.071
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: rs11025887; hg19: chr11-21062974;