11-21372313-C-T

Position:

• chr11-21372313-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000357134.10(NELL1):​c.1645+1365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,464 control chromosomes in the GnomAD database, including 10,093 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 0.36 (10093 hom., cov: 31)
• Consequence: NELL1 ENST00000357134.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NELL1	NM_006157.5	c.1645+1365C>T		intron_variant		ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.1729+1365C>T		intron_variant			NP_001275642.1
NELL1	NM_001288714.1	c.1474+1365C>T		intron_variant			NP_001275643.1
NELL1	NM_201551.2	c.1645+1365C>T		intron_variant			NP_963845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.1645+1365C>T		intron_variant		1	NM_006157.5	ENSP00000349654	P1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54268 AN: 151354 Hom.: 10081 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.359 AC: 54306 AN: 151464 Hom.: 10093 Cov.: 31 AF XY: 0.358 AC XY: 26445 AN XY: 73956

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.358

Alfa AF: 0.370 Hom.: 9620

Bravo AF: 0.375

Asia WGS AF: 0.338 AC: 1167 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.065
DANN	Benign	0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7120820; hg19: chr11-21393859;