chr11-21524590-T-C

Variant names:

• chr11-21524590-T-C
• rs4614448
• NM_006157.5:c.1646-9784T>C

Variant summary

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

The NM_006157.5(NELL1):​c.1646-9784T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 151,980 control chromosomes in the GnomAD database, including 55,612 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 0.84 (55612 hom., cov: 30)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1646-9784T>C		intron_variant	Intron 15 of 19	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1730-9784T>C		intron_variant	Intron 16 of 20		NP_001275642.1
NELL1	NM_201551.2	c.1646-35599T>C		intron_variant	Intron 15 of 18		NP_963845.1
NELL1	NM_001288714.1	c.1475-9784T>C		intron_variant	Intron 14 of 18		NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.1646-9784T>C		intron_variant	Intron 15 of 19	1	NM_006157.5	ENSP00000349654.5

Frequencies

GnomAD3 genomes AF: 0.842 AC: 127870 AN: 151862 Hom.: 55592 Cov.: 30

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.842 AC: 127934 AN: 151980 Hom.: 55612 Cov.: 30 AF XY: 0.844 AC XY: 62666 AN XY: 74288

African (AFR) AF: 0.607 AC: 25128 AN: 41388

American (AMR) AF: 0.925 AC: 14124 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3336 AN: 3470

East Asian (EAS) AF: 0.787 AC: 4058 AN: 5158

South Asian (SAS) AF: 0.799 AC: 3827 AN: 4790

European-Finnish (FIN) AF: 0.956 AC: 10132 AN: 10596

Middle Eastern (MID) AF: 0.918 AC: 268 AN: 292

European-Non Finnish (NFE) AF: 0.946 AC: 64344 AN: 67988

Other (OTH) AF: 0.855 AC: 1806 AN: 2112

Alfa AF: 0.918 Hom.: 259308

Bravo AF: 0.832

Asia WGS AF: 0.785 AC: 2731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.26
PhyloP100		-0.29
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: rs4614448; hg19: chr11-21546136;