rs73469144

Variant names:

• chr11-21483354-A-C
• rs73469144
• NM_006157.5:c.1646-51020A>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.1646-51020A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 152,180 control chromosomes in the GnomAD database, including 1,011 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 0.091 (1011 hom., cov: 31)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488
• Publications: 3 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 = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1646-51020A>C		intron_variant	Intron 15 of 19	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1730-51020A>C		intron_variant	Intron 16 of 20		NP_001275642.1
NELL1	NM_201551.2	c.1646-76835A>C		intron_variant	Intron 15 of 18		NP_963845.1
NELL1	NM_001288714.1	c.1475-51020A>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.1646-51020A>C		intron_variant	Intron 15 of 19	1	NM_006157.5	ENSP00000349654.5

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13790 AN: 152062 Hom.: 1010 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0754

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.0791

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

GnomAD4 genome AF: 0.0906 AC: 13792 AN: 152180 Hom.: 1011 Cov.: 31 AF XY: 0.0882 AC XY: 6565 AN XY: 74410

African (AFR) AF: 0.198 AC: 8229 AN: 41490

American (AMR) AF: 0.0753 AC: 1150 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3468

East Asian (EAS) AF: 0.0502 AC: 260 AN: 5184

South Asian (SAS) AF: 0.0574 AC: 277 AN: 4826

European-Finnish (FIN) AF: 0.0421 AC: 447 AN: 10620

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0435 AC: 2958 AN: 68002

Other (OTH) AF: 0.0802 AC: 169 AN: 2108

Alfa AF: 0.0728 Hom.: 262

Bravo AF: 0.0994

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.077
DANN	Benign	0.39
PhyloP100		-0.49
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: rs73469144; hg19: chr11-21504900;