11-21073410-A-G

Variant names:

• chr11-21073410-A-G
• rs7924855
• NM_006157.5:c.1301-40179A>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.1301-40179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,958 control chromosomes in the GnomAD database, including 27,728 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 0.60 (27728 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1301-40179A>G		intron_variant	Intron 12 of 19	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1385-40179A>G		intron_variant	Intron 13 of 20		NP_001275642.1
NELL1	NM_201551.2	c.1301-40179A>G		intron_variant	Intron 12 of 18		NP_963845.1
NELL1	NM_001288714.1	c.1130-40179A>G		intron_variant	Intron 11 of 18		NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.1301-40179A>G		intron_variant	Intron 12 of 19	1	NM_006157.5	ENSP00000349654.5

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91539 AN: 151840 Hom.: 27702 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.603 AC: 91621 AN: 151958 Hom.: 27728 Cov.: 32 AF XY: 0.601 AC XY: 44657 AN XY: 74258

African (AFR) AF: 0.556 AC: 23028 AN: 41428

American (AMR) AF: 0.607 AC: 9256 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2194 AN: 3470

East Asian (EAS) AF: 0.618 AC: 3184 AN: 5148

South Asian (SAS) AF: 0.551 AC: 2660 AN: 4824

European-Finnish (FIN) AF: 0.615 AC: 6495 AN: 10554

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42731 AN: 67960

Other (OTH) AF: 0.610 AC: 1285 AN: 2108

Alfa AF: 0.619 Hom.: 49445

Bravo AF: 0.602

Asia WGS AF: 0.641 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.22
PhyloP100		-0.76
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: rs7924855; hg19: chr11-21094956;